Abnormal B-cell regulation in highly sensitized patients with sustained serum levels of antibody to HLA class I antigens

BACKGROUND: There are anti-idiotypes in the sera of highly sensitized (HS) patients that stimulate B cells to produce antibody to HLA class I antigens. The purpose of this study is to determine if there is an abnormality in B cell responses to these anti-idiotypes. METHODS: Supernatants from normal and HS B cells exposed to either HLA-like anti-idiotypes or HS sera were tested for IgG and antibody to HLA class I antigens by ELISA and flow beads. RESULTS: When stimulated with HS sera, HS B cells produced antibody to HLA class I antigens (in vitro) (12/12) but normal B cells did not (0/10) (P<0.0001). When HS B cells were stimulated with isolated HLA-like anti-idiotypes, they produced more total IgG in the supernatant (603+/-105 ng/ml vs. 293+/-30 ng/ml; P<0.01) and more IgG1 (67+/-5.3 ng/ml vs. 32.3+/-5.4 ng/ml; P<0.001) and more IgG3 (33.3+/-9.2 vs. 2.03+/-0.2 ng/ml; P<0.0001) than normal B cells. The proliferative response to HLA-like anti-idiotypes was 1285+/-115 cpm from normal B cells and 1020+/-445 from HS B cells (p=NS). CONCLUSIONS: When exposed to HS sera, HS B cells produced antibody to HLA class I antigens and normal B cells did not. When exposed to isolated HLA-like anti-idiotypes, HS B cells produced more total IgG, primarily IgG1 and IgG3 with normal proliferation. This intrinsic abnormality in HS B cells permits antibody to HLA class I antigens to be produced and allows increased amounts of IgG1 and IgG3 to be secreted in the absence of an increase in proliferation.