title: Abnormal B-cell regulation in highly sensitized patients with sustained serum levels of antibody to HLA class I antigens.
abstract: 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.
authors.affiliation: Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Nashrudeen
authors.initials: N
authors.lastname: Hack
authors.forename: Sarita
authors.initials: S
authors.lastname: Angra
authors.forename: Theresa L
authors.initials: TL
authors.lastname: McKnight
authors.forename: Neal
authors.initials: N
authors.lastname: den Hollander
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Cardella
mesh_terms: D000906:Antibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology*; D001769:Blood; D049109:Cell Proliferation; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D008297:Male
chemical_list: D000906:Antibodies; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes