期刊
FRONTIERS IN IMMUNOLOGY
卷 7, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2016.00643
关键词
retinoic acid; B cell; peritoneum; marginal zone; immunoglobulins
类别
资金
- Welcome Trust [091823/z/10/z]
- Medical Research Council (MRC) Centre for Transplantation, King's College London
- National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust and King's College London
- UK-MRC [MR/J006742/1]
- Wellcome Trust [091823/Z/10/Z] Funding Source: Wellcome Trust
- MRC [G0802068] Funding Source: UKRI
- Medical Research Council [MR/J006742/1] Funding Source: researchfish
Retinoic acid (RA) plays an important role in the balance of inflammation and tolerance in T cells. Furthermore, it has been demonstrated that RA facilitates IgA isotype switching in B cells in vivo. However, it is unclear whether RA has a direct effect on T-independent B cell responses in vivo. To address this question, we generated a mouse model where RA signaling is specifically silenced in the B cell lineage. This was achieved through the overexpression of a dominant negative receptor a for RA (dnRAR alpha) in the B cell lineage. In this model, we found a dramatic reduction in marginal zone (MZ) B cells and accumulation of transitional 2 B cells in the spleen. We also observed a reduction in B1 B cells in the peritoneum with a defect in the T-independent B cell response against 2,4,6-trinitrophenyl. This was not a result of inhibited development of B cells in the bone marrow, but likely the result of both defective expression of S1P(1) in MZ B cells and a defect in the development of MZ and B1 B cells. This suggests that RAR alpha expression in B cells is important for B cell frequency in the MZ and peritoneum, which is crucial for the generation of T-independent humoral responses.
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