CD45 links the B cell receptor with cell survival and is required for the persistence of germinal centers

Nicholas D. Huntington, Yuekang Xu, Hamsa Puthalakath, Amanda Light, Simon N. Willis, Andreas Strasser, David M. Tarlinton

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60 Citations (Scopus)

Abstract

To segregate the many contributions that B cell receptor (BCR)-mediated signals make to immune responses, we have analyzed here B cells deficient in the 'pan-leukocyte' marker CD45. BCR ligation of Cd45-I- B cells failed to activate phosphatidylinositol-3-OH kinase, NF-κB, Erk1 or Erk2 kinases or to upregulate cell survival proteins and instead induced apoptosis. Immunization of Cd45-I- B cell chimeras induced germinal centers and antigen-specific immunoglobulin G1 antibody-forming cells early, but both cellular compartments decreased by day 14. Proliferation of Cd45-I- B cells induced by CD40 ligand in vitro was impaired as a result of abrogation by BCR ligation of the upregulation of prosurvival proteins. In contrast, enforced expression of the antiapoptotic factor Bcl-xL prevented the collapse of Cd45-I- B cell germinal centers. These results show mechanistic differences in B cell survival during germinal center initiation and propagation; CD40 signaling is sufficient for the former, whereas the latter requires signaling from the BCR.

Original languageEnglish
Pages (from-to)190-198
Number of pages9
JournalNature Immunology
Volume7
Issue number2
DOIs
Publication statusPublished - 1 Feb 2006
Externally publishedYes

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