期刊
JOURNAL OF IMMUNOLOGY
卷 181, 期 5, 页码 3373-3383出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.5.3373
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资金
- American Cancer Society Scholar [RSG-02-172-LIB]
- Roche Organ Transplantation Research Foundation [111662730]
- National Institutes of Health [R01 A 1064826-01, U19 A1062627-01, NO1-HHSN26600500032C, HL-45100]
- American Heart Association [SDG0235127N]
- The American Society for Blood and Marrow Transplantation Young Investigator Award
Rapt is a small GTPase that belongs to Ras superfamily. This ubiquitously expressed GTPase is a key regulator of integrin functions. Rap1 exists in two isoforms: Rap1a and Rap1b. Although Rap1 has been extensively studied, its isoform-specific functions in B cells have not been elucidated. In this study, using gene knockout mice, we show that Rap1b is the dominant isoform in B cells. Lack of Rap1b significantly reduced the absolute number of B220(+)IgM(-) pro/pre-B cells and B220(+)IgM(+) immature B cells in bone marrow. In vitro culture of bone marrow-derived Rap1b(-/-) pro/pre-B cells with IL-7 showed similar proliferation levels but reduced adhesion to stromal cell line compared with wild type. Rap1b(-/-) mice displayed reduced splenic marginal zone (MZ) B cells, and increased newly forming B cells, whereas the number of follicular B cells was normal. Functionally, Rap1b(-/-) mice showed reduced T-dependent but normal T-independent Immoral responses. B cells from Raplb-/- mice showed reduced migration to SDF-1, CXCL13 and in vivo homing to lymph nodes. MZ B cells showed reduced sphingosine-I-phosphate-induced migration and adhesion to ICAM-1. However, absence of Rap1b did not affect splenic B cell proliferation, BCR-mediated activation of Erk1/2, p38 MAPKs, and AKT. Thus, Rap1b is crucial for early B cell development, MZ B cell homeostasis and T-dependent Immoral immunity.
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