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Blood, 1 July 2007, Vol. 110, No. 1, pp. 193-200.
Prepublished online as a Blood First Edition Paper on March 14, 2007; DOI 10.1182/blood-2006-07-038414.
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Submitted July 28, 2006
Accepted February 26, 2007
The in vivo function of a non-canonical TRAF2 binding domain in the C-terminus of CD40 in driving B cell growth and differentiation
Li-Fan Lu, Cory L Ahonen, Evan F Lind, Vanitha S Raman, W. James Cook, Ling-Li Lin, and Randolph J Noelle*
Dept of Microbiology & Immunology, Dartmouth Medical School & the Norris Cotton Cancer Center, Lebanon, NH
* Corresponding author; email: rjn{at}dartmouth.edu.
The recruitment of tumor necrosis factor receptor-associated factors (TRAFs) 1,2,3,5 and 6 to the CD40 cytoplasmic tail upon CD40 trimerization results in downstream signaling events that ultimately lead to CD40-dependent, thymus-dependent (TD) humoral immune responses. Previously, we have shown signaling through the C-terminal tail of CD40 in the absence of canonical TRAF binding sites are capable of signaling through an alternative TRAF2 binding site. Here, we demonstrate that B cells from mice harboring CD40 with only the C-terminal tail can activate both canonical and non-canonical NF B signaling pathways. Moreover, while lacking germinal center formation, several hallmarks of humoral immune responses including clonal B cell activation/expansion, antibody isotype switching, and affinity maturation remain normal. This study demonstrates a new functional domain in CD40 which controls critical aspects of B cell immunity in an in vivo setting.
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[Abstract]
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