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 elements of the BCR-signaling cascade. We now show that cross-linking also blocks the processing and presentation of BCR-bound Ag. This occurs because the Fc gamma RII isoform typically expressed by B cells (Fc gamma RII-B1) is incompetent for endocytosis. When cross-linked, Fc gamma RII-B1 acts as a dominant negative inhibitor of BCR endocytosis. In contrast, cross-linking of endocytosis-competent Fc gamma RII isoforms did not inhibit endocytosis or processing of BCR-bound Ag. Thus, Fc gamma RII-B1 acts not only to prevent B cell activation under conditions of Ab excess, but also to prevent clonotypic T cell activation by inhibiting the ability of B cells to generate specific MHC class II-bound TCR ligands.
Minskoff
S A
SA
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
Matter
K
K
Mellman
I
I
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000378:metabolism; D000941:Antigens / Q000378:metabolism*; D015703:Antigens, CD / Q000502:physiology*; D002460:Cell Line; D004705:Endocytosis / Q000276:immunology; D000939:Epitopes / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism*; D017452:Receptors, IgG / Q000502:physiology*
D000936:Antigen-Antibody Complex; D000941:Antigens; D015703:Antigens, CD; D000939:Epitopes; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG