FcgammaRIIB regulates autoreactive primary antibody-forming cell, but not germinal center B cell, activity.
The low-affinity FcR for IgG FcgammaRIIB suppresses the development of IgG autoantibodies and autoimmune disease in normal individuals, but how this effect is mediated is incompletely understood. To investigate this issue, we created FcgammaRIIB-deficient versions of two previously described targeted BCR-transgenic lines of mice that contain follicular B cells with specificity for the hapten arsonate, but with different levels of antinuclear autoantigen reactivity. The primary development and tolerance of both types of B cells were unaltered by the absence of FcgammaRIIB. Moreover, the reduced p-azophenylarsonate-driven germinal center and memory responses characteristic of the highly autoreactive clonotype were not reversed by an intrinsic FcgammaRIIB deficiency. In contrast, the p-azophenylarsonate-driven primary Ab-forming cell responses of both clonotypes were equivalently increased by such a deficiency. In total, our data do not support the idea that FcgammaRIIB directly participates in the action of primary or germinal center tolerance checkpoints. In contrast, this receptor apparently contributes to the prevention of autoimmunity by suppressing the production of autoreactive IgGs from B cells that have breached tolerance checkpoints and entered the Ab-forming cell pathway due to spontaneous, or cross-reactive, Ag-mediated activation.
Rahman
Ziaur S M
ZS
Department of Microbiology and Immunology and Kimmel Cancer Center, Thomas Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107, USA. zrahman@mail.jci.tju.edu
Alabyev
Boris
B
Manser
Tim
T
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D000074462:Positive Regulatory Domain I-Binding Factor 1; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D000941:Antigens; D001323:Autoantibodies; C499172:Fcgr2b protein, mouse; D007143:Immunoglobulin Heavy Chains; C513258:Prdm1 protein, mouse; D017452:Receptors, IgG; D012097:Repressor Proteins; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1