期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 13, 期 4, 页码 451-461出版社
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/cmi.2015.18
关键词
viability; apoptosis; internalization; BCR; surface plasmon resonance analysis (SPRA); wild type (WT); B cell receptor (BCR); co-immunoprecipitation (co-IP); room temperature (RT); annexin V(A); eFluor (eF)
类别
资金
- FWF projects [P-24543, P-22419, W1213]
Deletion of HAX1 in mice causes a severe reduction in the numbers of lymphocytes in the bone marrow and in the spleen. Additionally, B220(+) B progenitor cells in the bone marrow are reduced, suggesting an important function of HAX1 in B cell development. HAX1 is thought to play a protective role in apoptotic processes; therefore, we investigated the role of HAX1 in bone marrow B progenitor cells and splenic B cells. We did not observe an effect on the survival of Hax1(-/-) bone marrow cells but detected enhanced survival of splenic Hax1(-/-) B cells upon in vitro starvation/growth-factor withdrawal. To explain this apparent inconsistency with previous reports of HAX1 function, we also studied the B cell receptor (BCR)-induced apoptosis of IgM-stimulated splenic naive B cells and found that apoptosis decreased in these cells. We further found impaired internalization of the BCR from Hax1(-/-) splenic B cells after IgM crosslinking; this impaired internalization may result in decreased BCR signaling and, consequently, decreased BCR-mediated apoptosis. We measured HAX1 binding to the cytoplasmic domains of different Ig subtypes and identified KVKWI(V) F as the putative binding motif for HAX1 within the cytoplasmic domains. Because this motif can be found in almost all Ig subtypes, it is likely thatHAX1 plays a general role in BCR-mediated internalization events and BCR-mediated apoptosis.
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