Roles of membrane domains in the signaling pathway for B cell survival

Miki Yokoyama, Tomoko Kimura, Sachio Tsuchida, Hiroaki Kaku, Kiyoshi Takatsu, Yoshio Hirabayashi, Masaki Yanagishita

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


B cell response to antigens forms the basis for humoral immune responses. Mature B cells are rescued from spontaneous apoptosis in the presence of survival factors such as anti-IgM antibody, LPS, and anti-CD40 antibody. This in vitro rescue correlates with in vivo B-cell proliferation and differentiation induced by thymus-independent (TI) -2, TI-1, and thymus-dependent (TD) antigens. Crosslinking of B cell receptor (BCR) by anti-IgM antibody promotes a positive feedback loop in the vicinity of BCR to activate those tyrosine kinases, Syk and Btk, crucial for the NF-γB activation. Ligation of CD40 triggers a recruitment of IγB kinase through TNF receptor-activated factors (TRAFs). Sphingolipid- and cholesterol-enriched membrane domains are important for the assembly of the signaling molecules during TI-2 and TD antigens recognition. B cells can be rescued from apoptosis even in the absence of antigen by an agonistic antibody (anti-CD38 antibody), CS/2. An absolute requirement of Syk and Btk in the CS/2 action suggests that an intracellular signaling pathway of CS/2 is similar to that induced by BCR-crosslinking. However, the action of CS/2 does not elicit appreciable tyrosine phosphorylation. Our data implies that CS/2 induces a conformational change of CD38 within the membrane domains, which leads to a generation of sphingolipid-mediated B cell survival signal.

Original languageEnglish
Title of host publicationSphingolipid Biology
PublisherSpringer Japan
Number of pages7
ISBN (Print)4431341986, 9784431341987
Publication statusPublished - 2006
Externally publishedYes


  • B cell receptor
  • B cell survival
  • CD38
  • Membrane domains


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