High-density expression of CD95 on B cells and underrepresentation of the B-1 cell subset in human lupus

Recent evidence indicates that B cell receptor signaling plays a role in the generation of the B-1 cell lineage that expresses the CD5 marker, and the CD95-mediated death plays an essential role in maintaining B cell tolerance. We therefore probed CD5 and CD95 expression on B cells from systemic lupus erythematosos (SLE) patients and control subjects. Firstly, in agreement with previous studies, we found that CD5 expression (11%) was relatively constant among control individuals. We also noted that the activation of B cells up-regulates this marker. Unexpectedly, we found that the B-1 cell subset is under-represented (3.9+/-0.3%) in SLE patients in an inactive stage of the disease. Together with related studies, these findings suggest that there is a correlation between CD5 expression and disease activity. Secondly, we found that CD95(+) B cells can be divided into two subsets expressing a high- (CD95(high)) and a low-density (CD95(low)) of CD95. There was no difference in the proportion of total CD95(+) B cells (23.5+/-2.8) in the two groups, but SLE patients in an inactive phase of the disease characteristically expressed a relatively high proportion (50%) of CD95(high) B cells. This finding would mean that a large fraction of B lymphocytes are sensitive to apoptosis, implying that autoantibody-producing B cells are derived from CD95(low) B cells and are relatively resistant to apoptosis.