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Retinoic acid regulates mouse B‐cell activation and differentiation induced by engagement of CD40, B‐cell antigen receptor and cytokine IL‐4
Author(s) -
Chen Qiuyan,
Ross A. Catharine
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a737-c
Subject(s) - cd40 , b cell , cell growth , microbiology and biotechnology , t cell , cytokine , chemistry , retinoic acid , b cell receptor , biology , immune system , immunology , cell culture , cytotoxic t cell , antibody , biochemistry , in vitro , genetics
All trans‐Retinoic acid (RA) is an important regulator for the immune system, but its role in B‐cell activation is unclear. To study how RA regulates B‐cell activation and early differentiation, we have used a model of purified mouse splenic B cells stimulated by ligation of CD40 (a surrogate of T cell co‐stimulation), and treatment with IL‐4, a principal Th‐2 cytokine, along with the B‐cell antigen receptor (BCR). CD40 engagement or IL‐4 alone induced B‐cell activation indicated by increased cell proliferation, Ig γ1 germline transcripts (γ1 GLT), and surface (s)IgG1 expression, while triple stimulation with anti‐CD40/anti‐μ/IL‐4 synergized to heighten B‐cell activation. RA (20 nM) was growth inhibitory for anti‐CD40/anti‐μ‐activated B cells, but did not inhibit cell proliferation in the presence of IL‐4. Whereas RA reduced γ1 GLT expression induced by CD40 ligation and IL‐4, it up‐regulated sIgG1 at both condition. Flow cytometry showed that triple stimulation including RA increased the proportion of mature B cells that were larger in size, had undergone fewer division cycles, and were enriched for γ1 GLT and sIgG1. These results suggest that CD40 and IL‐4 may use different signaling pathways at the early phase of B‐cell activation. RA regulates B‐cell activation in a complex manner, as it inhibited the early cell proliferation and γ1 GLT level, it simultaneously promoted the formation of sIgG1 expressing cells.