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

Jiancheng Hu, Shannon K. Oda, Kristin Shotts, Erin E. Donovan, Pamela Strauch, Lindsey M. Pujanauski, Francisco Victorino, Amin Al-Shami, Yuko Fujiwara, Gabor Tigyi, Tamas Oravecz, Roberta Pelanda, Raul M. Torres

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)85-95
Number of pages11
JournalJournal of Immunology
Volume193
Issue number1
DOIs
StatePublished - Jul 1 2014

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Lysophosphatidic Acid Receptors
Lysophospholipids
B-Cell Antigen Receptors
Antibody Formation
B-Lymphocytes
Inositol 1,4,5-Trisphosphate Receptors
Chemotactic Factors
Adaptive Immunity
Humoral Immunity
Signal Transduction
Lymphocytes
Calcium
Infection
lysophosphatidic acid
Neoplasms

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Hu, J., Oda, S. K., Shotts, K., Donovan, E. E., Strauch, P., Pujanauski, L. M., ... Torres, R. M. (2014). Lysophosphatidic acid receptor 5 inhibits B cell antigen receptor signaling and antibody response. Journal of Immunology, 193(1), 85-95. https://doi.org/10.4049/jimmunol.1300429

Lysophosphatidic acid receptor 5 inhibits B cell antigen receptor signaling and antibody response. / Hu, Jiancheng; Oda, Shannon K.; Shotts, Kristin; Donovan, Erin E.; Strauch, Pamela; Pujanauski, Lindsey M.; Victorino, Francisco; Al-Shami, Amin; Fujiwara, Yuko; Tigyi, Gabor; Oravecz, Tamas; Pelanda, Roberta; Torres, Raul M.

In: Journal of Immunology, Vol. 193, No. 1, 01.07.2014, p. 85-95.

Research output: Contribution to journalArticle

Hu, J, Oda, SK, Shotts, K, Donovan, EE, Strauch, P, Pujanauski, LM, Victorino, F, Al-Shami, A, Fujiwara, Y, Tigyi, G, Oravecz, T, Pelanda, R & Torres, RM 2014, 'Lysophosphatidic acid receptor 5 inhibits B cell antigen receptor signaling and antibody response', Journal of Immunology, vol. 193, no. 1, pp. 85-95. https://doi.org/10.4049/jimmunol.1300429
Hu, Jiancheng ; Oda, Shannon K. ; Shotts, Kristin ; Donovan, Erin E. ; Strauch, Pamela ; Pujanauski, Lindsey M. ; Victorino, Francisco ; Al-Shami, Amin ; Fujiwara, Yuko ; Tigyi, Gabor ; Oravecz, Tamas ; Pelanda, Roberta ; Torres, Raul M. / Lysophosphatidic acid receptor 5 inhibits B cell antigen receptor signaling and antibody response. In: Journal of Immunology. 2014 ; Vol. 193, No. 1. pp. 85-95.
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