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Nat Immunol. 2006 Feb;7(2):190-8. Epub 2005 Dec 25.

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

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The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.


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-/- B cells failed to activate phosphatidylinositol-3-OH kinase, NF-kappaB, Erk1 or Erk2 kinases or to upregulate cell survival proteins and instead induced apoptosis. Immunization of Cd45-/- 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-/- 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-/- 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.

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