Signal transduction through Vav-2 participates in humoral immune responses and B cell maturation

Abstract

B and T lymphocytes develop normally in mice lacking the guanine nucleotide exchange factor Vav-2. However, the immune responses to type II thymus-independent antigen as well as the primary response to thymus-dependent (TD) antigen are defective. Vav-2-deficient mice are also defective in their ability to switch immunoglobulin class, form germinal centers and generate secondary immune responses to TD antigens. Mice lacking both Vav-1 and Vav-2 contain reduced numbers of B lymphocytes and display a maturational block in the development of mature B cells. B cells from Vav-1(-/-)Vav-2(-/-) mice respond poorly to antigen receptor triggering, both in terms of proliferation and calcium release. These studies show the importance of Vav-2 in humoral immune responses and B cell maturation.

Transitional Type 1 and 2 B Lymphocyte Subsets Are Differentially Responsive to Antigen Receptor Signaling

“…In separate studies, we have shown that at least two components of the BCR signalosome, BTK and PLC-␥2, are required for the activation of NF-B and transcriptional up-regulation of the bcl-x gene (58), 2 further supporting an involvement of the BCR signaling in T2 B cell responses. Like BTK and PLC-␥2, other components of the BCR signalosome including phosphatidylinositol 3-kinase, Vav, and B cell linker protein are involved in the transition of immature B cells to more mature stages (27,28,40,(42)(43)(44)(45). The opposite biological responses of T1 versus T2 and an involvement of the BCR signaling components in this process is also supported by a recent study published during the preparation of this manuscript (65).…”

Differential role of SLP-76 domains in T cell development and function

“…The block in SLP-76 ⌬2-156 mice could be due to the inability of the SLP-76 mutant to recruit members of the Vav, Itk and͞or Nck families, and͞or additional proteins that may interact with the SLP-76 N-terminal domain (2-4). Neither disruption of individual or dual combinations of the Vav proteins Vav1 and Vav 2 (19)(20)(21)(22), nor of the Tec kinases Itk, Tec, and Rlk͞Txk (23, 24) blocks T cell development at the DN stage.…”

Transcriptional Factor Aryl Hydrocarbon Receptor (Ahr) Controls Cardiovascular and Respiratory Functions by Regulating the Expression of the Vav3 Proto-oncogene

“…Animal Use-Ahr and Vav3 knock-out mice have been reported previously (25,38,45 (45,47,48), and Vav3 Ϫ/Ϫ mice and subsequent homogenization in the BL10 genetic background. Unless otherwise stated, 4-month-old mice were used in experiments.…”