TY - JOUR
T1 - FcγRIIB regulates autoreactive primary antibody-forming cell, but not germinal center B cell, activity
AU - Rahman, Ziaur S.M.
AU - Alabyev, Boris
AU - Manser, Tim
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2007/1/15
Y1 - 2007/1/15
N2 - The low-affinity FcR for IgG FcγRIIB suppresses the development of IgG antoantibodies and autoimmune disease in normal individuals, but how this effect is mediated is incompletely understood. To investigate this issue, we created FcγRIIB-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 FcγRIIB. Moreover, the reduced p-azophenylarsonate-driven germinal center and memory responses characteristic of the highly autoreactive clonotype were not reversed by an intrinsic FcγRIIB 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 FcγRIIB 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.
AB - The low-affinity FcR for IgG FcγRIIB suppresses the development of IgG antoantibodies and autoimmune disease in normal individuals, but how this effect is mediated is incompletely understood. To investigate this issue, we created FcγRIIB-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 FcγRIIB. Moreover, the reduced p-azophenylarsonate-driven germinal center and memory responses characteristic of the highly autoreactive clonotype were not reversed by an intrinsic FcγRIIB 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 FcγRIIB 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.
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U2 - 10.4049/jimmunol.178.2.897
DO - 10.4049/jimmunol.178.2.897
M3 - Article
C2 - 17202351
AN - SCOPUS:33846245118
SN - 0022-1767
VL - 178
SP - 897
EP - 907
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -