Therapeutic targeting of CD19 in hematological malignancies: Past, present, future and beyond

Leukemia and Lymphoma

Volumn 55, Issue 5, 2014, Pages 999-1006

  Katz, Ben Zion ^a,b   Herishanu, Yair ^a  

^a TEL AVIV SOURASKY MEDICAL CENTER   (Israel)

^b TEL AVIV UNIVERSITY   (Israel)

Author keywords

Antibodies; B cell; CD19

Indexed keywords

B LYMPHOCYTE RECEPTOR; BRUTON TYROSINE KINASE; CD19 ANTIGEN; CD20 ANTIGEN; CD79B ANTIGEN; CD81 ANTIGEN; COMMON ACUTE LYMPHOBLASTIC LEUKEMIA ANTIGEN; COMPLEMENT COMPONENT C3D RECEPTOR; GROWTH FACTOR RECEPTOR BOUND PROTEIN 2; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN KINASE LYN; PROTEIN KINASE SYK; SOS PROTEIN; ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY;

ACUTE LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTIGEN EXPRESSION; B CELL LEUKEMIA; CELL AGGREGATION; CHRONIC LYMPHATIC LEUKEMIA; ENZYME ACTIVATION; GENE MUTATION; HEMATOLOGIC MALIGNANCY; HUMAN; IMMUNORECEPTOR TYROSINE BASED ACTIVATION MOTIF; INTRACELLULAR SIGNALING; LARGE CELL LYMPHOMA; NATURAL KILLER CELL; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW; T CELL LEUKEMIA; TUMOR MICROENVIRONMENT; ANIMAL; CELL TRANSFORMATION; CLINICAL TRIAL (TOPIC); DRUG SCREENING; GENE EXPRESSION REGULATION; GENETICS; HEMATOLOGIC NEOPLASMS; IMMUNOLOGY; MOLECULARLY TARGETED THERAPY;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIGENS, CD19; ANTINEOPLASTIC AGENTS; CELL TRANSFORMATION, NEOPLASTIC; CLINICAL TRIALS AS TOPIC; DRUG EVALUATION, PRECLINICAL; GENE EXPRESSION REGULATION; HEMATOLOGIC NEOPLASMS; HUMANS; MOLECULAR TARGETED THERAPY;

EID: 84899753936     PISSN: 10428194     EISSN: 10292403     Source Type: Journal    
DOI: 10.3109/10428194.2013.828354     Document Type: Review

References (104)

1. Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med 2005; 352: 804-815.
2. Herishanu Y, Katz BZ, Lipsky A, et al. Biology of chronic lymphocytic leukemia in different microenvironments: Clinical and therapeutic implications. Hematol Oncol Clin North Am 2013; 27: 173-206.
3. Sachen KL, Strohman MJ, Singletary J, et al. Self-Antigen recognition by follicular lymphoma B-cell receptors. Blood 2012; 120: 4182-4190.
4. Zwick C, Fadle N, Regitz E, et al. Autoantigenic targets of B-cell receptors derived from chronic lymphocytic leukemias bind to and induce proliferation of leukemic cells. Blood 2013; 121: 4708-4717.
5. Ghia P, Chiorazzi N, Stamatopoulos K. Microenvironmental influences in chronic lymphocytic leukaemia: The role of antigen stimulation. J Intern Med 2008; 264: 549-562.
6. Davis R E, Ngo V N, Lenz G, et al. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 2010; 463: 88-92.
7. Duhren-von Minden M, Ubelhart R, Schneider D, et al. Chronic lymphocytic leukaemia is driven by antigen-independent cellautonomous signalling. Nature 2012; 489: 309-312.
8. Binder M, Muller F, Frick M, et al. CLL B-cell receptors can recognize themselves: Alternative epitopes and structural clues for autostimulatory mechanisms in CLL. Blood 2013; 121: 239-241.
9. Bradbury LE, Kansas GS, Levy S, et al. The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules. J Immunol 1992; 149: 2841-2850.
10. Carroll M C, Isenman D E. R egulation of humoral immunity by complement. Immunity 2012; 37: 199-207.
11. van Zelm MC, Smet J, Adams B, et al. CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. J Clin Invest 2010; 120: 1265-1274.
12. Chalupny NJ, Kanner SB, Schieven GL, et al. Tyrosine phosphorylation of CD19 in pre-B and mature B cells. EMBO J 1993; 12: 2691-2696.
13. Brooks SR, Li X, Volanakis EJ, et al. Systematic analysis of the role of CD19 cytoplasmic tyrosines in enhancement of activation in Daudi human B cells: Clustering of phospholipase C and Vav and of Grb2 and Sos with different CD19 tyrosines. J Immunol 2000; 164: 3123-3131.
14. Brooks SR, Kirkham PM, Freeberg L, et al. Binding of cytoplasmic proteins to the CD19 intracellular domain is high affi nity, competitive, and multimeric. J Immunol 2004; 172: 7556-7564.
15. Fujimoto M, Fujimoto Y, Poe J C, et a l. C D19 regulates Src family protein tyrosine kinase activation in B lymphocytes through processive amplification. Immunity 2000; 13: 47-57.
16. Wang Y, Brooks SR, Li X, et al. The physiologic role of CD19 cytoplasmic tyrosines. Immunity 2002; 17: 501-514.
17. Herishanu Y, Kay S, Dezorella N, et al. Divergence in CD19-mediated signaling unfolds intraclonal diversity in chronic lymphocytic leukemia, which correlates with disease progression. J Immunol 2013; 190: 784-793.
18. Matsumoto AK, Martin DR, Carter RH, et al. Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes. J Exp Med 1993; 178: 1407-1417.
19. Bradbury LE, Goldmacher VS, Tedder TF. The CD19 signal transduction complex of B lymphocytes. Deletion of the CD19 cytoplasmic domain alters signal transduction but not complex formation with TAPA-1 and Leu 13. J Immunol 1993; 151: 2915-2927.
20. Carter RH, Myers R. Germinal center structure and function: Lessons from CD19. Semin Immunol 2008; 20: 43-48.
21. Hoellenriegel J, Meadows SA, Sivina M, et al. The phosphoinositide 3 '-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood 2011; 118: 3603-3612.
22. Burger J A, Hoellenriegel J. P hosphoinositide 3'-kinase delta: Turning off BCR signaling in chronic lymphocytic leukemia. Oncotarget 2011; 2: 737-738.
23. Chung EY, Psathas JN, Yu D, et al. CD19 is a major B cell receptorindependent activator of MYC-driven B-lymphomagenesis. J Clin Invest 2012; 122: 2257-2266.
24. Poe JC, Minard-Colin V, Kountikov EI, et al. A c-Myc and surface CD19 signaling amplification loop promotes B cell lymphoma development and progression in mice. J Immunol 2012; 189: 2318-2325.
25. Nadler LM, Anderson KC, Marti G, et al. B4, ahuman B lymphocyteassociated antigen expressed on normal, mitogen-Activated, and malignant B lymphocytes. J Immunol 1983; 131: 244-250.
26. Nadler LM, Korsmeyer SJ, Anderson KC, et al. B cell origin of non-T cell acute lymphoblastic leukemia. A model for discrete stages of neoplastic and normal pre-B cell differentiation. J Clin Invest 1984; 74: 332-340.
27. van Zelm MC, van der Burg M, de Ridder D, et al. Ig gene rearrangement steps are initiated in early human precursor B cell subsets and correlate with specific transcription factor expression. J Immunol 2005; 175: 5912-5922.
28. Ciudad J, Orfao A, Vidriales B, et al. Immunophenotypic analysis of CD19-precursors in normal human adult bone marrow: Implications for minimal residual disease detection. Haematologica 1998; 83: 1069-1075.
29. Simmons S, Knoll M, Drewell C, et al. Biphenotypic B-lymphoid/ myeloid cells expressing low levels of Pax5: Potential targets of BAL development. Blood 2012; 120: 3688-3698.
30. Otero DC, Rickert RC. CD19 function in early and late B cell development. II. CD19 facilitates the pro-B/pre-B transition. J Immunol 2003; 171: 5921-5930.
31. Bene M C, Nebe T, Bettelheim P, et al. Immunophenotyping of acute leukemia and lymphoproliferative disorders: A consensus proposal of the European LeukemiaNet Work Package 10. Leukemia 2011; 25: 567-574.
32. van Dongen JJ, Lhermitte L, Bottcher S, et al. EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia 2012; 26: 1908-1975.
33. Perez-Andres M, Paiva B, Nieto WG, et al. Human peripheral blood B-cell compartments: A crossroad in B-cell traffic. Cytometry B Clin Cytom 2010; 78(Suppl. 1): S47-S60.
34. Ginaldi L, De Martinis M, Matutes E, et al. Levels of expression of CD19 and CD20 in chronic B cell leukaemias. J Clin Pathol 1998; 51: 364-369.
35. Ocqueteau M, Orfao A, Almeida J, et al. Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients. Implications for the differential diagnosis between MGUS and multiple myeloma. Am J Pathol 1998; 152: 1655-1665.
36. Mateo G, Montalban MA, Vidriales MB, et al. Prognostic value of immunophenotyping in multiple myeloma: A study by the PETHEMA/ GEM cooperative study groups on patients uniformly treated with high-dose therapy. J Clin Oncol 2008; 26: 2737-2744.
37. Chaidos A, Barnes CP, Cowan G, et al. Clinical drug resistance linked to interconvertible phenotypic and functional states of tumorpropagating cells in multiple myeloma. Blood 2013; 121: 318-328.
38. Kim D, Park C Y, Medeiros B C, et a l. C D19-CD45 low/-CD38 high/ CD138-plasma cells enrich for human tumorigenic myeloma cells. Leukemia 2012; 26: 2530-2537.
39. Hosen N, Matsuoka Y, Kishida S, et a l. C D138-negative clonogenic cells are plasma cells but not B cells in some multiple myeloma patients. Leukemia 2012; 26: 2135-2141.
40. Seegmiller AC, Xu Y, McKenna RW, et al. Immunophenotypic differentiation between neoplastic plasma cells in mature B-cell lymphoma vs plasma cell myeloma. Am J Clin Pathol 2007; 127: 176-181.
41. Olteanu H, Wang H Y, Chen W, et al. Immunophenotypic studies of monoclonal gammopathy of undetermined significance. BMC Clin Pathol 2008; 8: 13.
42. Boucher K, Parquet N, Widen R, et al. Stemness of B-cell progenitors in multiple myeloma bone marrow. Clin Cancer Res 2012; 18: 6155-6168.
43. Bataille R, Jego G, Robillard N, et a l. The phenotype of normal, reactive and malignant plasma cells. Identification of ' many and multiple myelomas ' and of new targets for myeloma therapy. Haematologica 2006; 91: 1234-1240.
44. Francis J, Dharmadhikari A V, Sait S N, et a l. C D19 expression in acute leukemia is not restricted to the cytogenetically aberrant populations. Leuk Lymphoma 2013; 54: 1517-1520.
45. Walter K, Cockerill PN, Barlow R, et al. Aberrant expression of CD19 in AML with t(8;21) involves a poised chromatin structure and PAX5. Oncogene 2010; 29: 2927-2937.
46. Tiacci E, Pileri S, Orleth A, et al. PAX5 expression in acute leukemias: Higher B-lineage specificity than CD79a and selective association with t(8;21)-Acute myelogenous leukemia. Cancer Res 2004; 64: 7399-7404.
47. Rizzo K, Stetler-Stevenson M, Wilson W, et al. Novel CD19 expression in a peripheral T cell lymphoma: A flow cytometry case report with morphologic correlation. Cytometry B Clin Cytom 2009; 76: 142-149.
48. Weinberg O K, Arber D A. M ixed-phenotype acute leukemia: Historical overview and a new definition. Leukemia 2010; 24: 1844-1851.
49. Weir EG, Ali Ansari-Lari M, Batista DA, et al. Acute bilineal leukemia: A rare disease with poor outcome. Leukemia 2007; 21: 2264-2270.
50. May R D, Vitetta E S, Moldenhauer G, et al. Selective killing of normal and neoplastic human B cells with anti-CD19-And anti-CD22-ricin A chain immunotoxins. Cancer Drug Deliv 1986; 3: 261-272.
51. Uckun FM, Gajl-Peczalska KJ, Kersey JH, et al. Use of a novel colony assay to evaluate the cytotoxicity of an immunotoxin containing pokeweed antiviral protein against blast progenitor cells freshly obtained from patients with common B-lineage acute lymphoblastic leukemia. J Exp Med 1986; 163: 347-368.
52. Ghetie MA, May RD, Till M, et al. Evaluation of ricin A chaincontaining immunotoxins directed against CD19 and CD22 antigens on normal and malignant human B-cells as potential reagents for in vivo therapy. Cancer Res 1988; 48: 2610-2617.
53. Bregni M, Siena S, Formosa A, et a l. B-cell restricted saporin immunotoxins: Activity against B-cell lines and chronic lymphocytic leukemia cells. Blood 1989; 73: 753-762.
54. Uckun FM, Chelstrom LM, Finnegan D, et al. effective immunochemotherapy of CALLA-C mu-human pre-B acute lymphoblastic leukemia in mice with severe combined immunodeficiency using B43 (anti-CD19) pokeweed antiviral protein immunotoxin plus cyclophosphamide. Blood 1992; 79: 3116-3129.
55. Uckun FM, Manivel C, Arthur D, et al. In vivo efficacy of B43 (anti-CD19)-pokeweed antiviral protein immunotoxin against human pre-B cell acute lymphoblastic leukemia in mice with severe combined immunodeficiency. Blood 1992; 79: 2201-2214.
56. Grossbard ML, Lambert JM, Goldmacher VS, et al. Correlation between in vivo toxicity and preclinical in vitro parameters for the immunotoxin anti-B4-blocked ricin. Cancer Res 1992; 52: 4200-4207.
57. Ghetie M A, Tucker K, Richardson J, et a l. The antitumor activity of an anti-CD22 immunotoxin in SCID mice with disseminated Daudi lymphoma is enhanced by either an anti-CD19 antibody or an anti-CD19 immunotoxin. Blood 1992; 80: 2315-2320.
58. Jansen B, Kersey JH, Jaszcz WB, et al. effective immunochemotherapy of human t(4;11) leukemia in mice with severe combined immunodeficiency (SCID) using B43 (anti-CD19)-pokeweed antiviral protein immunotoxin plus cyclophosphamide. Leukemia 1993; 7: 290-297.
59. Watanabe M, Pesando JM, Hakomori S. effect of liposomes containing sodium butyrate conjugated with anti-CD19 monoclonal antibody on in vitro and in vivo growth of malignant lymphoma. Cancer Res 1990; 50: 3245-3248.
60. Bonardi MA, Bell A, French RR, et al. Initial experience in treating human lymphoma with a combination of bispecific antibody and saporin. Int J Cancer Suppl 1992; 7: 73-77.
61. Grossbard ML, Freedman AS, Ritz J, et al. Serotherapy of B-cell neoplasms with anti-B4-blocked ricin: A phase I trial of daily bolus infusion. Blood 1992; 79: 576-585.
62. Multani PS, O ' Day S, Nadler LM, et al. Phase II clinical trial of bolus infusion anti-B4 blocked ricin immunoconjugate in patients with relapsed B-cell non-Hodgkin's lymphoma. Clin Cancer Res 1998; 4: 2599-2604.
63. Grossbard ML, Fidias P, Kinsella J, et al. Anti-B4-blocked ricin: A phase II trial of 7 day continuous infusion in patients with multiple myeloma. Br J Haematol 1998; 102: 509-515.
64. Younes A, Kim S, Romaguera J, et al. Phase I multidose-escalation study of the anti-CD19 maytansinoid immunoconjugate SAR3419 administered by intravenous infusion every 3 weeks to patients with relapsed/refractory B-cell lymphoma. J Clin Oncol 2012; 30: 2776-2782.
65. Furman R R, Grossbard M L, Johnson J L, et a l. A phase III study of anti-B4-blocked ricin as adjuvant therapy post-Autologous bone marrow transplant: CALGB 9254. Leuk Lymphoma 2011; 52: 587-596.
66. Pizer B, Papanastassiou V, Hancock J, et al. A pilot study of monoclonal antibody targeted radiotherapy in the treatment of central nervous system leukaemia in children. Br J Haematol 1991; 77: 466-472.
67. Vuist WM, vBuitenen F, de Rie MA, et al. Potentiation by interleukin 2 of Burkitt's lymphoma therapy with anti-pan B (anti-CD19) monoclonal antibodies in a mouse xenotransplantation model. Cancer Res 1989; 49: 3783-3788.
68. Vuist WM, van Buitenen F, Hekman A, et al. Two distinct mechanisms of antitumor activity mediated by the combination of interleukin 2 and monoclonal antibodies. Cancer Res 1990; 50: 5767-5772.
69. Hekman A, Honselaar A, Vuist WM, et al. Initial experience with treatment of human B cell lymphoma with anti-CD19 monoclonal antibody. Cancer Immunol Immunother 1991; 32: 364-372.
70. Kvalheim G, Sorensen O, Fodstad O, et al. Immunomagnetic removal of B-lymphoma cells from human bone marrow: A procedure for clinical use. Bone Marrow Transplant 1988; 3: 31-41.
71. De Rosa L, Montuoro A, Pandolfi A, et al. Immunomagnetic purging procedure for autologous bone marrow transplantation in lymphoid malignancies. Haematologica 1991; 76(Suppl. 1): 37-40.
72. Rhodes EG, Baker P, Rhodes JM, et al. Peanut agglutinin in combination with CD19 monoclonal antibody has potential as a purging agent in myeloma. Exp Hematol 1991; 19: 833-837.
73. Matlawska-Wasowska K, Ward E, Stevens S, et al. Macrophage and NK-mediated killing of precursor-B acute lymphoblastic leukemia cells targeted with a-fucosylated anti-CD19 humanized antibodies. Leukemia 2013; 27: 1263-1274.
74. Cardarelli PM, Rao-Naik C, Chen S, et al. A nonfucosylated human antibody to CD19 with potent B-cell depletive activity for therapy of B-cell malignancies. Cancer Immunol Immunother 2010; 59: 257-265.
75. Horton H M, Bernett M J, Pong E, et al. Potent in vitro and in vivo activity of an Fc-engineered anti-CD19 monoclonal antibody against lymphoma and leukemia. Cancer Res 2008; 68: 8049-8057.
76. Awan FT, Lapalombella R, Trotta R, et al. CD19 targeting of chronic lymphocytic leukemia with a novel Fc-domain-engineered monoclonal antibody. Blood 2010; 115: 1204-1213.
77. Zalevsky J, Leung IW, Karki S, et al. The impact of Fc engineering on an anti-CD19 antibody: Increased Fcgamma receptor affi nity enhances B-cell clearing in nonhuman primates. Blood 2009; 113: 3735-3743.
78. Cochlovius B, Kipriyanov SM, Stassar MJ, et al. Cure of Burkitt's lymphoma in severe combined immunodeficiency mice by T cells, tetravalent CD3-CD19 tandem diabody, and CD28 costimulation. Cancer Res 2000; 60: 4336-4341.
79. Bargou R, Leo E, Zugmaier G, et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science 2008; 321: 974-977.
80. Topp MS, Gokbuget N, Zugmaier G, et al. Long-Term followup of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood 2012; 120: 5185-5187.
81. Topp MS, Kufer P, Gokbuget N, et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol 2011; 29: 2493-2498.
82. Handgretinger R, Zugmaier G, Henze G, et al. Complete remission after blinatumomab-induced donor T-cell activation in three pediatric patients with post-Transplant relapsed acute lymphoblastic leukemia. Leukemia 2011; 25: 181-184.
83. Kochenderfer J N, Wilson W H, Janik J E, et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood 2010; 116: 4099-4102.
84. Kalos M, Levine BL, Porter DL, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 2011; 3: 95ra73.
85. Porter DL, Levine BL, Kalos M, et al. Chimeric antigen receptormodifi ed T cells in chronic lymphoid leukemia. N Engl J Med 2011; 365: 725-733.
86. Brentjens R J, Riviere I, Park J H, et al. Safety and persistence of adoptively transferred autologous CD19-Targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood 2011; 118: 4817-4828.
87. Brentjens RJ, Davila ML, Riviere I, et al. CD19-Targeted T cells rapidly induce molecular remissions in adults with chemotherapyrefractory acute lymphoblastic leukemia. Sci Transl Med 2013; 5: 177ra38.
88. Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptormodifi ed T cells for acute lymphoid leukemia. N Engl J Med 2013; 368: 1509-1518.
89. Jena B, Maiti S, Huls H, et al. Chimeric antigen receptor (CAR)-specific monoclonal antibody to detect CD19-specific T cells in clinical trials. PLoS One 2013; 8: E57838.
90. De Oliveira SN, Wang J, Ryan C, et al. A CD19/Fc fusion protein for detection of anti-CD19 chimeric antigen receptors. J Transl Med 2013; 11: 23.
91. Davila ML, Kloss CC, Gunset G, et al. CD19 CAR-Targeted T cells induce long-Term remission and B cell aplasia in an immunocompetent mouse model of B cell acute lymphoblastic leukemia. PLoS One 2013; 8: E61338.
92. Yoshizaki A, Miyagaki T, DiLillo DJ, et al. Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature 2012; 491: 264-268.
93. Yanaba K, Bouaziz J D, Haas K M, et a l. A regulatory B cell subset with a unique CD1dhiCD5-phenotype controls T cell-dependent inflammatory responses. Immunity 2008; 28: 639-650.
94. Matsushita T, Yanaba K, Bouaziz JD, et al. Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J Clin Invest 2008; 118: 3420-3430.
95. Watanabe R, Ishiura N, Nakashima H, et al. Regulatory B cells (B10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbates systemic autoimmunity. J Immunol 2010; 184: 4801-4809.
96. van Zelm MC, Reisli I, van der Burg M, et al. An antibodydeficiency syndrome due to mutations in the CD19 gene. N Engl J Med 2006; 354: 1901-1912.
97. Vince N, Boutboul D, Mouillot G, et al. Defects in the CD19 complex predispose to glomerulonephritis, as well as IgG1 subclass deficiency. J Allergy Clin Immunol 2011; 127: 538-541.e1-5.
98. Mei H E, Schmidt S, Dorner T. R ationale of anti-CD19 immunotherapy: An option to target autoreactive plasma cells in autoimmunity. Arthritis Res Ther 2012; 14(Suppl. 5): S1.
99. Culton DA, Nicholas MW, Bunch DO, et al. Similar CD19 dysregulation in two autoantibody-Associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss. J Clin Immunol 2007; 27: 53-68.
100. Sato S, Hasegawa M, Fujimoto M, et al. Quantitative genetic variation in CD19 expression correlates with autoimmunity. J Immunol 2000; 165: 6635-6643.
101. Sato S, Fujimoto M, Hasegawa M, et a l. A ltered blood B lymphocyte homeostasis in systemic sclerosis: Expanded naive B cells and diminished but activated memory B cells. Arthritis Rheum 2004; 50: 1918-1927.
102. Tsuchiya N, Kuroki K, Fujimoto M, et a l. A ssociation of a functional CD19 polymorphism with susceptibility to systemic sclerosis. Arthritis Rheum 2004; 50: 4002-4007.
103. Liubchenko GA, Appleberry HC, Striebich CC, et al. Rheumatoid arthritis is associated with signaling alterations in naturally occurring autoreactive B-lymphocytes. J Autoimmun 2013; 40: 111-121.
104. Das A, Ellis G, Pallant C, et al. IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection. J Immunol 2012; 189: 3925-3935.