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


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 G?12/13-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.

SUBMITTER: Hu J 

PROVIDER: S-EPMC4128188 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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

Hu Jiancheng J   Oda Shannon K SK   Shotts Kristin K   Donovan Erin E EE   Strauch Pamela P   Pujanauski Lindsey M LM   Victorino Francisco F   Al-Shami Amin A   Fujiwara Yuko Y   Tigyi Gabor G   Oravecz Tamas T   Pelanda Roberta R   Torres Raul M RM  

Journal of immunology (Baltimore, Md. : 1950) 20140602 1


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  ...[more]

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