Antigen-induced Ca2+ signaling and desensitization in B cells

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

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Cross-linking of B cell surface Ig (sIg) by anti-Ig results in transmembrane signaling. However, the capacity of a thymus-dependent (TD) Ag to mediate B cell signal transduction has been less well documented. Therefore, we examined Ag-induced intracellular free calcium concentration ([Ca2+]) in B cells by using TD Ag that would be expected to either cross-link or not cross-link sIgM and/or induce the coupling of sIgM to FcR. Stimulation of mouse TA3 hybridoma B cell transfectants that express the SP6 anti-TNP specific sIgM with either TNO-OVA or anti-IgM antibodies resulted in a maximal fourfold increase in [Ca2+](i). The net increase in [Ca2+](i) in response to TNP-OVA was dependent upon both the Ag dose and the TNP:OVA molar ratio. Because occupancy of several cell-surface receptor types leads to a loss of response to subsequent stimulation by ligand (homologous desensitization), we examined the ability of Ag to induce homologous desensitization of sIgM in these B cells. TNP1-OVA at all concentrations tested (up to 500 μg/ml) did not lead to any change in [Ca2+](i) or desensitization. Cross-linking of TNP1-OVA (10 μg/ml) with F(ab')2 of anti-OVA antibody induced both a rise in [Ca2+](i) and homologous desensitization of sIg, suggesting that cross-linking of sIgM by Ag is sufficient to induce both these processes. TNP6-OVA at a concentration of 10 μg/ml induced changes in [Ca2+](i) and partially desensitized TNP-specific B cells to stimulation by anti-IgM. Interestingly, a high dose (180 μg/ml) of TNP6-OVA stimulated minimal changes in [Ca2+](i) yet did not lead to desensitization. However, cross-linking of TNP6-OVA at this high dose with F(ab')2 of rabbit anti-OVA elevated [Ca2+](i) and elicited partial desensitization. Complete desensitization of sIgM by Ag was achieved when intact (Fc-containing) anti-OVA antibody was used, suggesting that the FcR can play a role in desensitization. Ag- and antibody-mediated desensitization was not caused by steric hindrance of sIg. Thus, we have observed two forms of Ag-induced desensitization of sIgM, both of which involve sIg cross-linking and one of which is mediated by the physiologic coupling of sIg to FcR.

Original languageEnglish (US)
Pages (from-to)4147-4155
Number of pages9
JournalJournal of Immunology
Volume144
Issue number11
StatePublished - Jan 1 1990
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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