The in vivo balance between B cell clonal expansion and elimination is regulated by CD95 both on B cells and in their micro-environment.

Published

Journal Article

The expression of CD95 (Fas/APO-1) on B cells has been shown to play a direct role in their fate. B cells that chronically bind antigen due to prolonged antigen exposure, such as self-reactive B cells, are induced to express CD95 by CD40 ligand (CD40L) and are subsequently eliminated by CD95 ligand (CD95L) when they present antigen to CD4+ T cells. B cells that bind antigen acutely due to sudden antigen encounter, such as foreign antigen reactive B cells, up-regulate CD95, but are normally protected from CD95L-mediated apoptosis. Here, however, it is shown in vivo that foreign antigen-specific B cells fail to be protected from CD95-dependent elimination in a host that is CD95 deficient, regardless of antigenic challenge. These data indicate that B cell antigen receptor (BCR)-induced protection against CD95L-mediated apoptosis is not absolute but depends upon other micro-environmental factors in vivo. The normal balance between T cell-dependent humoral immunity and tolerance is thus regulated intrinsically by CD95 expression on responding B cells, and extrinsically by CD95-mediated control of CD95L or other molecules in the lymphoid micro-environment.

Full Text

Duke Authors

Cited Authors

  • Rathmell, JC; Goodnow, CC

Published Date

  • October 1998

Published In

Volume / Issue

  • 76 / 5

Start / End Page

  • 387 - 394

PubMed ID

  • 9797457

Pubmed Central ID

  • 9797457

International Standard Serial Number (ISSN)

  • 0818-9641

Digital Object Identifier (DOI)

  • 10.1046/j.1440-1711.1998.00774.x

Language

  • eng

Conference Location

  • United States