Short-circuiting long-lived humoral immunity by the heightened engagement of CD40.
Agonistic alpha CD40 Ab's have been shown to be potent immune adjuvants for both cell- and humoral-mediated immunity. While enhancing short-lived humoral immunity, the administration of a CD40 agonist during thymus-dependent immune responses ablates germinal center formation, prematurely terminates the humoral immune response, blocks the generation of B cell memory, and prevents the generation of long-lived bone marrow plasma cells. Interestingly, some of these effects of heightened CD40 engagement could be mimicked by enhancing the magnitude of antigen-specific T cell help. Taken together, these studies demonstrate that as the magnitude of CD40 signaling intensifies, the fate of antigen-reactive B cells can be dramatically altered. These are the first studies to describe the multifaceted function of CD40 in determining the fate of antigen-reactive B cells and provide novel insights into how CD40 agonists can short-circuit humoral immunity.
Erickson
Loren D
LD
Department of Microbiology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
Durell
Brigit G
BG
Vogel
Laura A
LA
O'Connor
Brian P
BP
Cascalho
Marilia
M
Yasui
Teruhito
T
Kikutani
Hitoshi
H
Noelle
Randolph J
RJ
D000818:Animals; D020296:Animals, Congenic; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051757:PAX5 Transcription Factor; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics
D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; C497282:Pax5 protein, mouse; C513258:Prdm1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1