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CD1d and CD1c Expression in Human B Cells Is Regulated by Activation and Retinoic Acid Receptor Signaling
- Source :
- The Journal of Immunology. 186:5261-5272
- Publication Year :
- 2011
- Publisher :
- The American Association of Immunologists, 2011.
-
Abstract
- B cell activation and Ab production in response to protein Ags requires presentation of peptides for recruitment of T cell help. We and others have recently demonstrated that B cells can also acquire innate help by presenting lipid Ags via CD1d to NKT cells. Given the newfound contribution of NKT cells to humoral immunity, we sought to identify the pathways that regulate CD1 molecule expression in human B cells. We show that ex vivo, activated and memory B cells expressed lower levels of CD1d compared with resting, naive, and marginal zone-like B cells. In vitro, CD1d was downregulated by all forms of B cell activation, leaving a narrow temporal window in which B cells could activate NKT cells. CD1c expression and function also decreased following activation by CD40L alone, whereas activation via the BCR significantly upregulated CD1c, particularly on marginal zone-like B cells. We found that the CD40L-induced downreglation of CD1d and CD1c correlated with diminished expression of retinoic acid receptor α (RARα) response genes, an effect that was reversed by RARα agonists. However, BCR-induced upregulation of CD1c was independent of the RAR pathway. Our findings that both CD1d and CD1c are upregulated by RARα signaling in human B cells is distinct from effects reported in dendritic cells, in which CD1c is inversely downregulated. One functional consequence of CD1d upregulation by retinoic acid was NKT cell cytotoxicity toward B cells. These results are central to our understanding of how CD1-restricted T cells may control humoral immunity.
- Subjects :
- Receptors, Retinoic Acid
T cell
Immunology
Naive B cell
B-cell receptor
CD1
Enzyme-Linked Immunosorbent Assay
chemical and pharmacologic phenomena
Cell Separation
Lymphocyte Activation
Antigens, CD1
medicine
Humans
Immunology and Allergy
Glycoproteins
Antigen Presentation
B-Lymphocytes
CD40
biology
Reverse Transcriptase Polymerase Chain Reaction
Retinoic Acid Receptor alpha
hemic and immune systems
Flow Cytometry
Natural killer T cell
Cell biology
Retinoic acid receptor
medicine.anatomical_structure
CD1D
biology.protein
Natural Killer T-Cells
Antigens, CD1d
Signal Transduction
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 186
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....40fce2a5a8a2ef3d6d75012343fa2769