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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.

Author information

1
Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA.
2
Lexicon Pharmaceuticals, Inc, The Woodlands, TX, 77381 USA.
3
Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
#
Contributed equally

Abstract

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.

PMID:
24890721
PMCID:
PMC4128188
DOI:
10.4049/jimmunol.1300429
[Indexed for MEDLINE]
Free PMC Article
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