Open AccessRetinoic Acid and α-Galactosylceramide Differentially Regulate B Cell ActivationIn Vitroand Augment Antibody ProductionIn Vivo
Author(s) -
Qiuyan Chen,
Kara L. Mosovsky,
A. Catharine Ross
Publication year - 2011
Publication title -
clinical and vaccine immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.649
H-Index - 77
eISSN - 1556-6811
pISSN - 1556-679X
DOI - 10.1128/cvi.00004-11
Subject(s) - b cell , antigen , biology , antibody , cd40 , cd1d , b 1 cell , t cell , antigen presenting cell , microbiology and biotechnology , immunology , immune system , chemistry , in vitro , cytotoxic t cell , natural killer t cell , biochemistry
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.