Lysophosphatidic acid receptor 5 inhibits B cell antigen receptor signaling and antibody response.

Autor:	Hu J; Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA., Oda SK; Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA., Shotts K; Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA., Donovan EE; Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA., Strauch P; Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA., Pujanauski LM; Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA., Victorino F; Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA., Al-Shami A; Lexicon Pharmaceuticals, Inc, The Woodlands, TX, 77381 USA.; Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA., Fujiwara Y; Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA., Tigyi G; Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA., Oravecz T; Lexicon Pharmaceuticals, Inc, The Woodlands, TX, 77381 USA., Pelanda R; Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA., Torres RM; Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2014 Jul 01; Vol. 193 (1), pp. 85-95. Date of Electronic Publication: 2014 Jun 02.
DOI:	10.4049/jimmunol.1300429
Abstrakt:	Lysophospholipids have emerged as biologically important chemoattractants capable of directing lymphocyte development, trafficking, and localization. Lysophosphatidic acid (LPA) is a major lysophospholipid found systemically, and its levels are elevated in certain pathological settings, such as cancer and infections. In this study, we demonstrate that BCR signal transduction by mature murine B cells is inhibited upon LPA engagement of the LPA5 (GPR92) receptor via a Gα12/13-Arhgef1 pathway. The inhibition of BCR signaling by LPA5 manifests by impaired intracellular calcium store release and most likely by interfering with inositol 1,4,5-triphosphate receptor activity. We further show that LPA5 also limits Ag-specific induction of CD69 and CD86 expression and that LPA5-deficient B cells display enhanced Ab responses. Thus, these data show that LPA5 negatively regulates BCR signaling, B cell activation, and immune response. Our findings extend the influence of lysophospholipids on immune function and suggest that alterations in LPA levels likely influence adaptive humoral immunity. (Copyright © 2014 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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