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The new B-cell-specific exon 1B of the CD5 mRNA favors autoimmunity by preventing the membrane expression of CD5
Arthritis Res Ther volume 5, Article number: 108 (2003)
Background and objective
The B-cell population comprises B1 and B2; the B1 population is subdivided into B1a, which express CD5, and B1b, which do not. B1 cells contribute to autoimmune disease, and a negative regulation has been ascribed to CD5. We recently described an alternative exon1 (referred as exon1B) and pursued the issue of the interplay of two exons 1 in the pathogenesis of lupus.
B cells, including the B1a, B1b and B2 subpopulations, and T cells, were sorted from periperal blood (PB), tonsils, cord blood (CB) and CLL samples. Jurkat and Daudi cells were used as positive and negative controls, respectively. Conventional, nested and real-time PCR, in situ hybridization and EBV transformation were used, and CD5 molecules were counted.
Exon 1B was shown to encode an additional mRNA in B cells and to be functional. It was never found in T cells, including those activated by anti-CD3 plus IL-2 or PMA. There was a gradient expression of exon 1A: PB T cells > B CLL > tonsil B (B1a > B1b > B2), > PB B > CB B cells. This correlated with the CD5 molecule at the membrane. In situ hybridization of cytospan cells and germinal center sections confirmed this statement. Exon 1A substituted to exon 1B in activated (anti-μ plus IL-2), but not in further advanced (anti-μ plus IL-4) B cells. The leader peptide of exon-1B-induced protein was hydrophilic (not expressed) while that of exon-1A-induced protein was hydrophobic (expressed).
An aberrant exon 1B usage prevents transportation of CD5 to the membrane. Given the negative control exerted by CD5 in the vicinity of the BCR, B-cell-mediated autoimmune disease might thus occur as a failure to express CD5.
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Renaudineau, Y., Haget, N., Le Goff, P. et al. The new B-cell-specific exon 1B of the CD5 mRNA favors autoimmunity by preventing the membrane expression of CD5. Arthritis Res Ther 5, 108 (2003) doi:10.1186/ar738
- Cord Blood
- Germinal Center
- Membrane Expression
- Leader Peptide
- Alternative Exon1