Retinoic acid and α-galactosylceramide differentially regulate B cell activation in vitro and augment antibody production in vivo

Qiuyan Chen, Kara L. Mosovsky, A. Catharine Ross

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1015-1020
Number of pages6
JournalClinical and Vaccine Immunology
Volume18
Issue number6
DOIs
StatePublished - Jun 2011

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

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