CD45 links the B cell receptor with cell survival and is required for the persistence of germinal centers.
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.
Huntington
Nicholas D
ND
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
Xu
Yuekang
Y
Puthalakath
Hamsa
H
Light
Amanda
A
Willis
Simon N
SN
Strasser
Andreas
A
Tarlinton
David M
DM
D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D002678:Chimera; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D066298:In Vitro Techniques; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction
D019013:CD40 Antigens; D011947:Receptors, Antigen, B-Cell; D019869:Phosphatidylinositol 3-Kinases; D017493:Leukocyte Common Antigens