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J Immunol. 2014 Jul 1;193(1):85-95. doi: 10.4049/jimmunol.1300429. Epub 2014 Jun 2.

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

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Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA.
Lexicon Pharmaceuticals, Inc, The Woodlands, TX, 77381 USA.
Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
Contributed equally


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.

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