B cells from M167 μκ transgenic mice fail to proliferate after stimulation with soluble anti-lg antibodies: A model for antigen-induced B cell anergy

D. G. Sieckmann, K. Holmes, P. Hornbeck, E. Martin, G. Guelde, S. Bondada, D. L. Longo, J. J. Kenny

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The transgenic (TG) mouse strain 207-4, carries μa + κ transgenes ligated to the anti-phosphocholine (PC) VH1 and Vκ24 V region genes from the MOPC-167 myeloma. Although B cells from mice carrying these transgenes respond both in vivo and in vitro to thymus-dependent Ags, they failed to proliferate in response to soluble goat anti-μ Ab or other soluble anti-lg reagents. On the other hand, B cells from the Sp6 μκ anti-trinitrophenyl TG mouse line proliferated normally after stimulation with soluble anti-μ. However, the 207-4 anti-PC transgene positive (TG+) splenic B cells proliferated when stimulated with anti-μ, anti-idiotype, anti-allotype, or PC-conjugated to Sepharose beads. TG+ B cells were also induced to proliferate when stimulated with anti-Lyb-2; thus, their defect may be restricted to signaling through slgM. The lack of response to soluble anti-μ could not be reversed by addition of IL-4, by removal of T cells, by addition of anti-FcR Ab, or by stimulation with F(ab')2 anti-μ. Thus, the failure to proliferate was not caused by active T cell suppression or FcR-mediated inhibition. In mixed cultures of TG+ and transgene negative (TG-) spleen cells, the TG- cells were able to proliferate normally to soluble anti-μ, indicating that suppressive factors were not involved in the unresponsiveness of the TG+ anti-PC-specific B cells. These studies suggest that B cells in the 207-4 anti-PC TG mice exhibit a defect in activation through their slgM receptors, and this unresponsiveness may reflect a form of Ag-induced tolerance.

Original languageEnglish
Pages (from-to)4873-4883
Number of pages11
JournalJournal of Immunology
Volume152
Issue number10
StatePublished - May 15 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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