title: Retinoic acid and α-galactosylceramide differentially regulate B cell activation in vitro and augment antibody production in vivo.
abstract: All-trans-retinoic acid (RA) promotes the maturation and differentiation of B cells, which are known as a type of professional antigen-presenting cells. We show here that CD1d, a major histocompatibility complex class I-like molecule that presents lipid antigens, is expressed in the mouse spleen B cells and is increased by RA. Thus, we hypothesized that RA and the CD1d ligand, α-galactosylceramide (αGalCer), could interact to promote the differentiation, maturation, and antibody response of antigen-activated B cells. In isolated B cells, αGalCer alone markedly stimulated, and RA further increased B cell proliferation, synergizing with the B cell antigen receptor ligation via anti-μ antibody (P < 0.05). The significantly increased cell proliferation stimulated by αGalCer was abrogated in the B cells of CD1d-null mice. RA alone and combined with αGalCer also promoted B cell differentiation by the enrichment of sIgG1-, CD138-, and PNA/Fas-positive B cells (P < 0.05), suggesting a plasmacytic cell differentiation. In vivo, wild-type mice treated with RA and/or αGalCer during primary immunization with tetanus toxoid produced a higher serum anti-tetanus IgG response and had more bone marrow anti-tetanus antibody-secreting cells as determined by enzyme-linked immunospot assay (P < 0.05) in the secondary response, a finding indicative of heightened long-term memory; however, the increased antibody secretion after αGalCer treatment was abolished in CD1d-null mice. We provide evidence here that RA, together with αGalCer, can effectively regulate B cell proliferation and differentiation, ultimately promoting a more efficient antibody response to protein antigen. The results suggest that the combination of RA and αGalCer could be a useful adjuvant combination in vaccine strategies.
authors.affiliation: Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Qiuyan
authors.initials: Q
authors.lastname: Chen
authors.forename: Kara L
authors.initials: KL
authors.lastname: Mosovsky
authors.forename: A Catharine
authors.initials: AC
authors.lastname: Ross
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation; D055610:Antigens, CD1d / Q000096:biosynthesis / Q000235:genetics; D000992:Antitoxins / Q000097:blood; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005699:Galactosylceramides / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology; D014212:Tretinoin / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D055610:Antigens, CD1d; D000992:Antitoxins; C526879:Cd1d1 protein, mouse; D005699:Galactosylceramides; D007074:Immunoglobulin G; D013745:Tetanus Toxoid; C493154:alpha-galactosylceramide; D014212:Tretinoin