Antigen-induced Fc receptor-dependent and -independent B cell desensitization: An elevation in [Ca2+](i) is not sufficient and protein kinase C activation is not required for these pathways of surface IgM-mediated desensitization

A. H. Lazarus, G. B. Mills, A. R. Crow, T. L. Delovitch

    Research output: Contribution to journalArticle

    8 Scopus citations

    Abstract

    The interaction of an Ag ligand with its B cell surface Ig (sIg) receptor can occur via an FcR-dependent or -independent pathway. We previously found that transfected TNP-specific B cells undergo both Ca2+ signaling and desensitization upon interaction with the thymus-dependent Ag TNP-OVA. Similarly, we showed that these B cells can also be desensitized by cross-linking sIg to the FcγR via the formation of an Ag-antibody bridge. Thus, Ag-specific B cells can be desensitized by two different Ag-dependent events, one mediated by Ag-sIg interaction and the other by sIg-FcγR cross-linking. Inasmuch as Ag-sIg and sIg-FcγR interactions lead to positive and negative signaling, it was of interest to determine whether B cell desensitization mediated by these interactions occurs by one of the well known signaling pathways in B cells. We found that Ag-induced changes in [Ca2+](i) could be readily dissociated from Ag-induced desensitization, indicating that a Ca2+-independent pathway is likely responsible for this pathway of desensitization. To determine if PKC plays a role in B cell desensitization mediated by either Ag or sIg-FcγR interaction, PKC was downregulated by long term exposure to 12-0-tetradecanoylphorbol 13-acetate or inhibited by exposure of cells to staurosporine. The PKC down-regulated and inhibited cells underwent similar Ag- and FcγR-dependent desensitization compared to cells containing active PKC. Taken together, these data indicate that Ag-induced desensitization of B cell signaling likely involves an event(s) that occurs either upstream or independent of Ag-induced elevations in [Ca2+](i) and PKC activation.

    Original languageEnglish (US)
    Pages (from-to)1739-1745
    Number of pages7
    JournalJournal of Immunology
    Volume147
    Issue number6
    StatePublished - Jan 1 1991

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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