Journal
JOURNAL OF IMMUNOLOGY
Volume 169, Issue 3, Pages 1145-1149Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.169.3.1145
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Funding
- NIAID NIH HHS [AI49993, AI28847] Funding Source: Medline
- NIDDK NIH HHS [DK25295] Funding Source: Medline
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Optimal Ag-specific B lymphocyte activation requires both recognition of Ag by the B cell Ag receptor (BCR) and contact-mediated interactions with Ag-specific Th lymphocytes. One of these interactions involves ligation of B cell CD40 by T cell-expressed CD154. CD40 signaling is crucial for Ab production, isotype switching, up-regulation of surface molecules, development of germinal centers, and the Immoral memory response. The signaling pathways emanating from the BCR and CD40 are able to cooperate, but the molecular mechanisms responsible for this interaction are incompletely understood. The present study explored the roles of signaling motifs in the CD40 cytoplasmic tail in this synergy. We find that threonine in the PXQXT motif in the TNFR-associated factor-2 binding site is critical for synergistic effects of CD40 and BCR signals, independent of its phosphorylation. Furthermore, data suggest an indirect role for TNFR-associated factor-2 in the cooperative signaling.
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