Inhibition of B-cell receptor-antigen complex internalization by Fc γRIIB1 signals

Abstract

Membrane-expressed immunoglobulins are B-cell receptors (BCR) for specific antigens (Ag). Upon Ag engagement of the BCR, B-cells are activated to internalize Ag-BCR complexes, process Ag and subsequently present Ag-peptides loaded in class II MHC. Due to the specific nature of the BCR, the cognate interaction between T-cells expressing Ag-specific T-cell receptor and these Ag-presenting B-cells occur in a highly regulated and precise manner. Accordingly, efficient control of T-cell activation may be achieved through regulation of Ag presenting B-cells. A potent form of regulation of lymphocyte responses is mediated by Ig end-product and anti-idiotypic antibodies via Fc-dependent mechanisms. In this communication, the authors present data that an anti-idiotype (anti-Id) Ab inhibits BCR-mediated internalization of specific Ag. Coupling of BCR to the cytoskeleton was also abortive in anti-Id Ab-treated B-cells. Inhibition by anti-Id Ab was dependent upon the presence of Fc γRIIB1 on B-cells. As a result of anti-Id Ab suppression, B-cells were unable to initiate Ca 2+responses in Ag-specific T-cells. The results suggest that co-crosslinking of Fc γRIIB1 and BCR inhibits cytoskeletal coupling and internalization of the Ag-BCR complex thereby preventing specific Ag presentation by B-cells. Anti-Id Ab may mediate a negative regulatory mechanism that suppresses B-cell-mediated Ag-specific T-cell activation.