CUTTING EDGE - FC-GAMMA-RII-B1 REGULATES THE PRESENTATION OF B-CELL RECEPTOR-BOUND ANTIGENS

Fc gamma receptors (Fc gamma RII) on B lymphocytes negatively regulate B cell receptor (BCR)-dependent activation upon cross-linking of the two receptors, The mechanism reflects the ability of the Fc gamma RII cytoplasmic tail to recruit specific phosphatases that inactivate elem ents of the BCR-signaling cascade. We now show that cross-linking also blocks the processing and presentation of BCR-bound Ag, This occurs b ecause the Fc gamma RII isoform typically expressed by B cells (Fc gam ma RII-B1) is incompetent for endocytosis, When cross-linked, Fc gamma RII-B1 acts as a dominant negative inhibitor of BCR endocytosis, In c ontrast, crosslinking of endocytosis-competent Fc gamma RII isoforms d id not inhibit endocytosis or processing of BCR-bound Ag, Thus, Fc gam ma RII-B1 acts not only to prevent B cell activation under conditions of Ab excess, but also to prevent clonotypic T cell activation by inhi biting the ability of B cells to generate specific MRC class II-bound TCR ligands.