title: 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 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.
authors.affiliation: Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA.
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Hu
authors.affiliation: Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA.
authors.forename: Shannon K
authors.initials: SK
authors.lastname: Oda
authors.affiliation: Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Shotts
authors.affiliation: Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Donovan
authors.affiliation: Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Strauch
authors.affiliation: Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA.
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Pujanauski
authors.affiliation: Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA.
authors.forename: Francisco
authors.initials: F
authors.lastname: Victorino
authors.affiliation: Lexicon Pharmaceuticals, Inc, The Woodlands, TX, 77381 USA.|Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
authors.forename: Amin
authors.initials: A
authors.lastname: Al-Shami
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
authors.forename: Gabor
authors.initials: G
authors.lastname: Tigyi
authors.affiliation: Lexicon Pharmaceuticals, Inc, The Woodlands, TX, 77381 USA.
authors.forename: Tamas
authors.initials: T
authors.lastname: Oravecz
authors.affiliation: Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA.
authors.forename: Roberta
authors.initials: R
authors.lastname: Pelanda
authors.affiliation: Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA.
authors.forename: Raul M
authors.initials: RM
authors.lastname: Torres
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000502:physiology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D056724:Immunity, Humoral / Q000502:physiology*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D051940:B7-2 Antigen; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D037181:Lectins, C-Type; D011947:Receptors, Antigen, B-Cell; D049368:Receptors, Lysophosphatidic Acid; D000099192:CD69 Antigens; C497965:Cd86 protein, mouse; C548235:LPAR5 protein, mouse