B-cell subsets imbalance and reduced expression of CD40 in ataxia-telangiectasia patients
Main Article Content
Keywords
Ataxia-telangiectasia, B cells, CD40, CD40L, IgM memory B cells, Switched memory B cells, CD21low
Abstract
Background: Ataxia-telangiectasia (AT) is a well-known primary immunodeficiency with recurrent sinopulmonary infections and variable abnormalities in both the humoral and cellular immune system. Dysfunctions in immunoglobulin production, reduced number of B cells, and B-cell receptor excision circles copies have been reported. We aimed to understand the immunological mechanisms involving the humoral compartment in AT patients by analysing peripheral blood B cells subsets, B-T lymphocyte cooperation through the expression of CD40 and CD40 ligand (CD40L), and cytokines involved in class-switch recombination production.
Methods: We compared the proportion of B-cell subsets, the expression of CD40/CD40L, and the plasma levels of IL-6 and IFN- of 18 AT patients and 15 healthy age-sex-matched controls using flow cytometry.
Results: We found that some steps in peripheral B cell development were altered in AT with a pronounced reduction of cell-surface CD40 expression. The proportions of transitional and naïve-mature B cells were reduced, whereas CD21-low, natural effector memory, IgM-only memory, and IgG atypical memory B cells were present in a higher proportion.
Conclusions: These findings revealed a disturbed B-cell homeostasis with unconventional maturation of B lymphocyte memory cells, which can explain the consequent impairment of humoral immunity.
References
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5. Lavin MF, Birrel G, Chen P, Kozlov S, Scott S, Gueven N. ATM signaling and genomic stability in response to DNA damage. Mutat Res. 2005;569:123-32.
6. McKinnon PJ. ATM and ataxia telangiectasia. Second in molecular medicine review series. EMBO Rep. 2004;5:772-6.
7. Picard C, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015;35:696-726.
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9. Schubert R, Reichenbach J, Zielen S. Deficiencies in CD4+ and CD8+ T cell subsets in ataxia-telangiectasia. Clin Exp Immunol. 2002;129:125-32.
10. Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, Carson KA, Lederman HM. Immunodeficiency and infections in ataxia-telangiectasia. J Pediatr. 2004;144:505-11.
11. Sanal O, Ersoy F, Yel L, Tezcan I, Metin A, Ozyürek H, et al. Impaired IgG antibody production to pneumoccocal polysaccharides in patients with ataxia-telangiectasia. J Clin Immunol. 1999;19:326-34.
12. Speck P, Ikeda M, Ikeda A, Lederman HM, Longnecker R. Signal transduction through the B cell antigen receptor is normal in ataxia-telangiectasia B lymphocytes. J Biol Chem. 2002;277:4123-7.
13. Borte S, von Döbeln U, Fasth A, Wang N, Janzi M, Winiarski J, et al. Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR. Blood. 2012;119:2552-5.
14. Mallott J, Kwan A, Church J, Gonzalez-Espinosa D, Lorey F, Tang LF, et al. Newborn screening for SCID identifies patients with ataxia-telangiectasia. J Clin Immunol. 2013;33:540-9.
15. Kraus M, Lev A, Simon AJ, Levran I, Nissenkorn A, Levi YB, et al. Disturbed B and T cell homeostasis and neogenesis in patients with ataxia-telangiectasia. J Clin Immunol. 2014;34:561-71.
16. Zhou BB, Elledge SJ. The DNA damage response: putting checkpoints in perspective. Nature. 2000;408:433-9.
17. Xu Y. DNA damage: a trigger of innate immunity but a requirement for adaptive immune homeostasis. Nat Rev Immunol. 2006;6:261-70.
18. Bredemeyer AL, Sharma GG, Huang CY, Helmink BA, Walker LM, Khor KC, et al. ATM stabilizes DNA double strand-break complexes during V(D)J recombination. Nature. 2006;442:466-70.
19. Reina-San-Martin B, Chen HT, Nussenzweig A, Nussenzweig MC. ATM is required for efficient recombination between immunoglobulin switch regions. J Exp Med. 2004;200:1103-10.
20. Staples ER, McDermott EM, Reiman A, Byrd PJ, Ritchie S, Taylor AM, et al. Immunodeficiency in ataxia-telangiectasia is correlated strongly with the presence of two null mutations in the ataxia-telangiectasia mutated gene. Clin Exp Immunol. 2008;153:214-20.
21. Available at: http://esid.org/Resources/Ataxia-Telangiectasia [accessed 04.10.16].
22. Berkowska MA, Driessen GJ, Bikos V, Grosserichter-Wagener C, Stamatopoulos K, Cerutti A, et al. Human memory B cells originates from three distinct germinal center-dependent and-independent maturation pathways. Blood. 2011;118:2150-8.
23. Seyama K, Nonoyama S, Gangsaas I, Hollenbaugh D, Pabst HF, Aruffo A, et al. Mutations of the CD40 ligand gene and its effect on CD40 ligand expression in patients with X-linked hyper IgM syndrome. Blood. 1998;92:2421-34.
24. Moraes-Pinto MI, Ono E, Santos-Valente ECS, Almeida LC, Andrade PR, Dinelli MIS, et al. Lymphocyte subsets in human immunodeficiency virus-unexposed Brazilian individuals form birth to adulthood. Mem Inst Oswaldo Cruz. 2014;109:989-98.
25. Chopra C, Davies G, Taylor M, Anderson M, Bainbridge S, Tighe P, et al. Immune deficiency in ataxia-telangiectasia: a longitudinal study of 44 patients. Clin Exp Immunol. 2014;176:275-82.
26. Bott L, Lebreton J, Thumerelle C, Cuvellier J, Deschildre A, Sardet A. Lung disease in ataxia-telangiectasia. Acta Paediatr. 2007;96:1021-4.
27. Bott L, Thumerelle C, Cuvellier JC, Deschildre A, Vallé L, Sardet A, et al. Arch Pediatr. 2006;13:293-8.
28. Schroeder SA, Zielen S. Infections of the respiratory system in patients with ataxia-telangiectasia. Pediatr Pulmonol. 2014;49:389-99.
29. Davies EG. Update on the management of the immunodeficiency in ataxia-telangiectasia. Expert Rev Clin Immunol. 2009;5:565-75.
30. Warnatz K, Denz A, Drager R, Braun M, Groth C, WolffVorbeck G, et al. Severe deficiency of switched memory B cells (CD27+ IgM−IgD−) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood. 2002;99:1544-51.
31. Piqueras B, Lavenu-Bombled C, Galicier L, Bergeron-van der Cruyssen F, Mouthon L, Chevret S, et al. Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects. J Clin Immunol. 2003;23:385-400.
32. Wehr C, Kivioja T, Schmitt C, Ferry B, Torsten W, Eren E, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008;111:77-85.
33. Shiloh Y, Lederman HM. Ataxia-telangiectasia (A-T): an emerging dimension of premature ageing. Ageing Res Rev. 2017;33:76-88.
34. Paganelli R, Scala E, Scarselli E, Ortolani C, Cossarizza A, Carmini D, et al. Selective deficiency of CD4+/CD45RA+ lymphocytes in patients with ataxia-telangiectasia. J Clin Immunol. 1992;12:84-91.
35. Exley AR, Buckenham S, Hodges E, Hallam R, Byrd P, Last J, et al. Premature ageing of the immune system underlies immunodeficiency in ataxia-telangiectasia. Clin Immunol. 2011;140: 26-36.
36. Bulati M, Buffa S, Candore G, Caruso C, Dunn-Walters DK, Pellicano M, et al. B cells and immunosenescence: a focus on IgG+IgD-CD27-(DN) B cells in aged humans. Ageing Res Rev. 2011;10:274-84.
37. Cancro MP, Hao Y, Scholz JL, Riley RL, Frasca D, Dunn-Walters DK, et al. B cells and ageing: molecules and mechanisms. Trends Immunol. 2009;30:313-8.
38. Frasca D, Blomberg BB. Aging affects human B cell responses. J Clin Immunol. 2011;31:430-5.
39. Klein U, Rajewsky K, Kuppers R. Human immunoglobulin (Ig)M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. J Exp Med. 1998;188:1679-89.
40. Agematsu K, Hokibara S, Nagumo H, Komiyama A. CD27: a memory B-cell marker. Immunol Today. 2000;21:204-6.
41. Colonna-Romano G, Bulati M, Aquino A, Pellicanò M, Vitello S, Lio D, et al. A double-negative (IgD−CD27−) B cell population is increased in the peripheral blood of elderly people. Mech Ageing Dev. 2009;130:681-90.
42. Buffa S, Bulati M, Pellicanò M, Dunn-Walters DK, Wu YC, Candore G, et al. B cell immunosenescence: different features of naïve and memory B cells in elderly. Biogerontology. 2011;12:473-83.
43. Shi Y, Yamazaki T, Okubo Y, Uehara Y, Sugane K, Agematsu K. Regulation of aged humoral immune defense against pneumococcal bacteria by IgM memory B cell. J Immunol. 2005;175:3262-7.
44. Weller S, Braun MC, Tan BK, Rosenwald A, Cordier C, Conley ME, et al. Human blood IgM ‘‘memory’’ B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. Blood. 2004;104:3647-54.
45. Agematsu K, Nagumo H, Shinozaki K, Hokibara S, Yasui K, Terada K, et al. Absence of IgD-CD27(+) memory B cell population in X-linked hyper-IgM syndrome. J Clin Invest. 1998;102:853-60.
46. Weller S, Faili A, Garcia C, Braun MC, Le Deist FF, de Saint Basile GG, et al. CD40-CD40L independent Ig gene hypermutation suggests a second B cell diversification pathway in humans. Proc Natl Acad Sci U S A. 2001;98:1166-70.
47. Carsetti R, Valentini D, Marcellini V, Scarsella M, Marasco E, Giustini F, et al. Reduced numbers of switched memory B cells with high terminal differentiation potential in Down syndrome. Eur J Immunol. 2015;45:903-14.
48. Freitas AA, Rocha B. Population biology of lymphocytes: the flight for survival. Annu Rev Immunol. 2000;18:83-111.
49. Isnardi I, Ng YS, Menard L, Meyers G, Saadoun D, Srdanovic I, et al. Complement receptor 2/CD21-human naïve B cells contain mostly autoreactive unresponsive clones. Blood. 2010;115:5026-36.
50. Rakhmanov M, Keller B, Gutenberger S, Foerster C, Hoenig M, Driessen G, et al. Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells. Proc Natl Acad Sci U S A. 2009;106:13451-6.
51. Rakhmanov M, Gutenberger S, Keller B, Schlesier M, Peter HH, Warnatz K. CD21low B cells in common variable immunodeficiency do not show defects in receptor editing, but resemble tissue-like memory B cells. Blood. 2010;116:3682-3.
52. Romberg N, Ng YS, Cunningham-Rundles C, Meffre E. Response: common variable immunodeficiency patients with increased CD21(-/lo) B cells suffer from altered receptor editing and defective central B-cell tolerance. Blood. 2011;118:5977-8.
53. Warnatz K, Wehr C, Dräger R, Schmidt S, Eibel H, Schlesier M, et al. Expansion of CD19(hi)CD21(lo/neg) B cells in common variable immunodeficiency(CVID) patients with autoimmune cytopenia. Immunobiology. 2002;206:502-13.
54. Thorarinsdottir K, Camponeschia A, Gjertsson I, Martensson IL. CD21-/low B cells: a snapshot of a unique B cell subset in health and disease. Scand J Immunol. 2015;82:254-61.
55. Driessen GJ, Ijspeert H, Weemaes CM, Haraldsson A, Trip M, Warris A, et al. Antibody deficiency in patients with ataxia-telangiectasia is caused by disturbed B- and T-cell homeostasis and reduced immune repertoire diversity. J Allergy Clin Immunol. 2013;131:1367-75.
56. Crotty S. A brief history of T cell help to B cells. Nat Rev Immunol. 2015;15:185-9.
57. Pallardó FV, Lloret A, Lebel M, d’Ischia M, Cogger VC, Le Couteur DG, et al. Mitochondrial dysfunction in some oxidative stress-related genetic diseases: ataxia-telangiectasia, Down syndrome, Fanconi anaemia and Werner syndrome. Biogerontology. 2010;11:401-19.
58. Andrade IG, Costa-Carvalho BT, da Silva R, Hix S, Kochi C, SuanoSouza FI, et al. Risk of atherosclerosis in patients with ataxia-telangiectasia. Ann Nutr Metab. 2015;66:196-201.
59. Reichenbach J, Schubert R, Schindler D, Muller K, Bohles H, Zielen S. Elevated oxidative stress in patients with ataxia telangiectasia. Antioxid Redox Signal. 2002;4:465-9.
60. McGrath-Morrow SA, Collaco JM, Crawford TO, Carson KA, Lefton-Greif MA, Zeitlin P, et al. Elevated serum IL-8 levels in ataxia-telangiectasia. J Pediatr. 2010;156:682-4.
61. Chiam LY, Verhagen MM, Haraldsson A, Wulffraat N, Driessen GJ, Netea MG, et al. Cutaneous granulomas in ataxia-telangiectasia and other primary immunodeficiencies: reflection of inappropriate immune regulation? Dermatology. 2011;223: 13-9.
62. Harbort CJ, Soeiro-Pereira PV, von Bernuth H, Kaindl AM, CostaCarvalho BT, Condino-Neto A, et al. Neutrophil oxidative burst activates ATM to regulate cytokine production and apoptosis. Blood. 2015;126:2842-51.
63. Chessa L, Leuzzi V, Plebani A, Soresina A, Micheli R, D’Agnano D, et al. Intra-erythrocyte infusion of dexamethasone reduces neurological symptoms in ataxia-telangiectasia patients: results of a phase 2 trial. Orphanet J Rare Dis. 2014;9:5.
2. Chun HH, Gatti RA. Ataxia-telangiectasia, an evolving phenotype. DNA Repair. 2004;3:1187-96.
3. Rotman G, Shiloh Y. ATM: from gene to function. Hum Mol Genet. 1998;7:1555-63.
4. Savistky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, et al. A single ataxia telangiectasia gene with similar to Pl-3 kinases. Science. 1995;268:1749-953.
5. Lavin MF, Birrel G, Chen P, Kozlov S, Scott S, Gueven N. ATM signaling and genomic stability in response to DNA damage. Mutat Res. 2005;569:123-32.
6. McKinnon PJ. ATM and ataxia telangiectasia. Second in molecular medicine review series. EMBO Rep. 2004;5:772-6.
7. Picard C, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015;35:696-726.
8. Claret Teruel G, Giner Munoz ˜ MT, Plaza Martín AM, Martín Mateos MA, Piquer Gibert M, Sierra Martínez JI. Variability of immunodeficiency associated with ataxia telangiectasia and clinical evolution in 12 affected patients. Pediatr Allergy Immunol. 2005;16:615-8.
9. Schubert R, Reichenbach J, Zielen S. Deficiencies in CD4+ and CD8+ T cell subsets in ataxia-telangiectasia. Clin Exp Immunol. 2002;129:125-32.
10. Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, Carson KA, Lederman HM. Immunodeficiency and infections in ataxia-telangiectasia. J Pediatr. 2004;144:505-11.
11. Sanal O, Ersoy F, Yel L, Tezcan I, Metin A, Ozyürek H, et al. Impaired IgG antibody production to pneumoccocal polysaccharides in patients with ataxia-telangiectasia. J Clin Immunol. 1999;19:326-34.
12. Speck P, Ikeda M, Ikeda A, Lederman HM, Longnecker R. Signal transduction through the B cell antigen receptor is normal in ataxia-telangiectasia B lymphocytes. J Biol Chem. 2002;277:4123-7.
13. Borte S, von Döbeln U, Fasth A, Wang N, Janzi M, Winiarski J, et al. Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR. Blood. 2012;119:2552-5.
14. Mallott J, Kwan A, Church J, Gonzalez-Espinosa D, Lorey F, Tang LF, et al. Newborn screening for SCID identifies patients with ataxia-telangiectasia. J Clin Immunol. 2013;33:540-9.
15. Kraus M, Lev A, Simon AJ, Levran I, Nissenkorn A, Levi YB, et al. Disturbed B and T cell homeostasis and neogenesis in patients with ataxia-telangiectasia. J Clin Immunol. 2014;34:561-71.
16. Zhou BB, Elledge SJ. The DNA damage response: putting checkpoints in perspective. Nature. 2000;408:433-9.
17. Xu Y. DNA damage: a trigger of innate immunity but a requirement for adaptive immune homeostasis. Nat Rev Immunol. 2006;6:261-70.
18. Bredemeyer AL, Sharma GG, Huang CY, Helmink BA, Walker LM, Khor KC, et al. ATM stabilizes DNA double strand-break complexes during V(D)J recombination. Nature. 2006;442:466-70.
19. Reina-San-Martin B, Chen HT, Nussenzweig A, Nussenzweig MC. ATM is required for efficient recombination between immunoglobulin switch regions. J Exp Med. 2004;200:1103-10.
20. Staples ER, McDermott EM, Reiman A, Byrd PJ, Ritchie S, Taylor AM, et al. Immunodeficiency in ataxia-telangiectasia is correlated strongly with the presence of two null mutations in the ataxia-telangiectasia mutated gene. Clin Exp Immunol. 2008;153:214-20.
21. Available at: http://esid.org/Resources/Ataxia-Telangiectasia [accessed 04.10.16].
22. Berkowska MA, Driessen GJ, Bikos V, Grosserichter-Wagener C, Stamatopoulos K, Cerutti A, et al. Human memory B cells originates from three distinct germinal center-dependent and-independent maturation pathways. Blood. 2011;118:2150-8.
23. Seyama K, Nonoyama S, Gangsaas I, Hollenbaugh D, Pabst HF, Aruffo A, et al. Mutations of the CD40 ligand gene and its effect on CD40 ligand expression in patients with X-linked hyper IgM syndrome. Blood. 1998;92:2421-34.
24. Moraes-Pinto MI, Ono E, Santos-Valente ECS, Almeida LC, Andrade PR, Dinelli MIS, et al. Lymphocyte subsets in human immunodeficiency virus-unexposed Brazilian individuals form birth to adulthood. Mem Inst Oswaldo Cruz. 2014;109:989-98.
25. Chopra C, Davies G, Taylor M, Anderson M, Bainbridge S, Tighe P, et al. Immune deficiency in ataxia-telangiectasia: a longitudinal study of 44 patients. Clin Exp Immunol. 2014;176:275-82.
26. Bott L, Lebreton J, Thumerelle C, Cuvellier J, Deschildre A, Sardet A. Lung disease in ataxia-telangiectasia. Acta Paediatr. 2007;96:1021-4.
27. Bott L, Thumerelle C, Cuvellier JC, Deschildre A, Vallé L, Sardet A, et al. Arch Pediatr. 2006;13:293-8.
28. Schroeder SA, Zielen S. Infections of the respiratory system in patients with ataxia-telangiectasia. Pediatr Pulmonol. 2014;49:389-99.
29. Davies EG. Update on the management of the immunodeficiency in ataxia-telangiectasia. Expert Rev Clin Immunol. 2009;5:565-75.
30. Warnatz K, Denz A, Drager R, Braun M, Groth C, WolffVorbeck G, et al. Severe deficiency of switched memory B cells (CD27+ IgM−IgD−) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood. 2002;99:1544-51.
31. Piqueras B, Lavenu-Bombled C, Galicier L, Bergeron-van der Cruyssen F, Mouthon L, Chevret S, et al. Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects. J Clin Immunol. 2003;23:385-400.
32. Wehr C, Kivioja T, Schmitt C, Ferry B, Torsten W, Eren E, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008;111:77-85.
33. Shiloh Y, Lederman HM. Ataxia-telangiectasia (A-T): an emerging dimension of premature ageing. Ageing Res Rev. 2017;33:76-88.
34. Paganelli R, Scala E, Scarselli E, Ortolani C, Cossarizza A, Carmini D, et al. Selective deficiency of CD4+/CD45RA+ lymphocytes in patients with ataxia-telangiectasia. J Clin Immunol. 1992;12:84-91.
35. Exley AR, Buckenham S, Hodges E, Hallam R, Byrd P, Last J, et al. Premature ageing of the immune system underlies immunodeficiency in ataxia-telangiectasia. Clin Immunol. 2011;140: 26-36.
36. Bulati M, Buffa S, Candore G, Caruso C, Dunn-Walters DK, Pellicano M, et al. B cells and immunosenescence: a focus on IgG+IgD-CD27-(DN) B cells in aged humans. Ageing Res Rev. 2011;10:274-84.
37. Cancro MP, Hao Y, Scholz JL, Riley RL, Frasca D, Dunn-Walters DK, et al. B cells and ageing: molecules and mechanisms. Trends Immunol. 2009;30:313-8.
38. Frasca D, Blomberg BB. Aging affects human B cell responses. J Clin Immunol. 2011;31:430-5.
39. Klein U, Rajewsky K, Kuppers R. Human immunoglobulin (Ig)M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. J Exp Med. 1998;188:1679-89.
40. Agematsu K, Hokibara S, Nagumo H, Komiyama A. CD27: a memory B-cell marker. Immunol Today. 2000;21:204-6.
41. Colonna-Romano G, Bulati M, Aquino A, Pellicanò M, Vitello S, Lio D, et al. A double-negative (IgD−CD27−) B cell population is increased in the peripheral blood of elderly people. Mech Ageing Dev. 2009;130:681-90.
42. Buffa S, Bulati M, Pellicanò M, Dunn-Walters DK, Wu YC, Candore G, et al. B cell immunosenescence: different features of naïve and memory B cells in elderly. Biogerontology. 2011;12:473-83.
43. Shi Y, Yamazaki T, Okubo Y, Uehara Y, Sugane K, Agematsu K. Regulation of aged humoral immune defense against pneumococcal bacteria by IgM memory B cell. J Immunol. 2005;175:3262-7.
44. Weller S, Braun MC, Tan BK, Rosenwald A, Cordier C, Conley ME, et al. Human blood IgM ‘‘memory’’ B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. Blood. 2004;104:3647-54.
45. Agematsu K, Nagumo H, Shinozaki K, Hokibara S, Yasui K, Terada K, et al. Absence of IgD-CD27(+) memory B cell population in X-linked hyper-IgM syndrome. J Clin Invest. 1998;102:853-60.
46. Weller S, Faili A, Garcia C, Braun MC, Le Deist FF, de Saint Basile GG, et al. CD40-CD40L independent Ig gene hypermutation suggests a second B cell diversification pathway in humans. Proc Natl Acad Sci U S A. 2001;98:1166-70.
47. Carsetti R, Valentini D, Marcellini V, Scarsella M, Marasco E, Giustini F, et al. Reduced numbers of switched memory B cells with high terminal differentiation potential in Down syndrome. Eur J Immunol. 2015;45:903-14.
48. Freitas AA, Rocha B. Population biology of lymphocytes: the flight for survival. Annu Rev Immunol. 2000;18:83-111.
49. Isnardi I, Ng YS, Menard L, Meyers G, Saadoun D, Srdanovic I, et al. Complement receptor 2/CD21-human naïve B cells contain mostly autoreactive unresponsive clones. Blood. 2010;115:5026-36.
50. Rakhmanov M, Keller B, Gutenberger S, Foerster C, Hoenig M, Driessen G, et al. Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells. Proc Natl Acad Sci U S A. 2009;106:13451-6.
51. Rakhmanov M, Gutenberger S, Keller B, Schlesier M, Peter HH, Warnatz K. CD21low B cells in common variable immunodeficiency do not show defects in receptor editing, but resemble tissue-like memory B cells. Blood. 2010;116:3682-3.
52. Romberg N, Ng YS, Cunningham-Rundles C, Meffre E. Response: common variable immunodeficiency patients with increased CD21(-/lo) B cells suffer from altered receptor editing and defective central B-cell tolerance. Blood. 2011;118:5977-8.
53. Warnatz K, Wehr C, Dräger R, Schmidt S, Eibel H, Schlesier M, et al. Expansion of CD19(hi)CD21(lo/neg) B cells in common variable immunodeficiency(CVID) patients with autoimmune cytopenia. Immunobiology. 2002;206:502-13.
54. Thorarinsdottir K, Camponeschia A, Gjertsson I, Martensson IL. CD21-/low B cells: a snapshot of a unique B cell subset in health and disease. Scand J Immunol. 2015;82:254-61.
55. Driessen GJ, Ijspeert H, Weemaes CM, Haraldsson A, Trip M, Warris A, et al. Antibody deficiency in patients with ataxia-telangiectasia is caused by disturbed B- and T-cell homeostasis and reduced immune repertoire diversity. J Allergy Clin Immunol. 2013;131:1367-75.
56. Crotty S. A brief history of T cell help to B cells. Nat Rev Immunol. 2015;15:185-9.
57. Pallardó FV, Lloret A, Lebel M, d’Ischia M, Cogger VC, Le Couteur DG, et al. Mitochondrial dysfunction in some oxidative stress-related genetic diseases: ataxia-telangiectasia, Down syndrome, Fanconi anaemia and Werner syndrome. Biogerontology. 2010;11:401-19.
58. Andrade IG, Costa-Carvalho BT, da Silva R, Hix S, Kochi C, SuanoSouza FI, et al. Risk of atherosclerosis in patients with ataxia-telangiectasia. Ann Nutr Metab. 2015;66:196-201.
59. Reichenbach J, Schubert R, Schindler D, Muller K, Bohles H, Zielen S. Elevated oxidative stress in patients with ataxia telangiectasia. Antioxid Redox Signal. 2002;4:465-9.
60. McGrath-Morrow SA, Collaco JM, Crawford TO, Carson KA, Lefton-Greif MA, Zeitlin P, et al. Elevated serum IL-8 levels in ataxia-telangiectasia. J Pediatr. 2010;156:682-4.
61. Chiam LY, Verhagen MM, Haraldsson A, Wulffraat N, Driessen GJ, Netea MG, et al. Cutaneous granulomas in ataxia-telangiectasia and other primary immunodeficiencies: reflection of inappropriate immune regulation? Dermatology. 2011;223: 13-9.
62. Harbort CJ, Soeiro-Pereira PV, von Bernuth H, Kaindl AM, CostaCarvalho BT, Condino-Neto A, et al. Neutrophil oxidative burst activates ATM to regulate cytokine production and apoptosis. Blood. 2015;126:2842-51.
63. Chessa L, Leuzzi V, Plebani A, Soresina A, Micheli R, D’Agnano D, et al. Intra-erythrocyte infusion of dexamethasone reduces neurological symptoms in ataxia-telangiectasia patients: results of a phase 2 trial. Orphanet J Rare Dis. 2014;9:5.
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Oct 15, 2018
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Pereira, C., Bichuetti-Silva, D., da Mota, N., Salomão, R., Brunialti, M., & Costa-Carvalho, B. (2018). B-cell subsets imbalance and reduced expression of CD40 in ataxia-telangiectasia patients. Allergologia Et Immunopathologia, 46(5), 438-446. https://all-imm.com/index.php/aei/article/view/376
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How to Cite
Pereira, C., Bichuetti-Silva, D., da Mota, N., Salomão, R., Brunialti, M., & Costa-Carvalho, B. (2018). B-cell subsets imbalance and reduced expression of CD40 in ataxia-telangiectasia patients. Allergologia Et Immunopathologia, 46(5), 438-446. https://all-imm.com/index.php/aei/article/view/376