The B cell repertoire of patients with rheumatoid arthritis. Frequencies and specificities of peripheral blood B cells reacting with human IgG, human collagens, a mycobacterial heat shock protein and other antigens.
Using a potent in vitro limiting dilution culture system, we have activated human peripheral blood B cells to proliferate and to differentiate into antibody-secreting cells (ASC). Under these conditions 25-100% of B cells are clonally expanded and produce IgM, IgG or IgA. Culture supernatants were tested for antibodies binding to human IgG-Fc fragments (RF), the 65-kD heat shock protein of Mycobacterium bovis (hsp60), human collagens type I, II, IV, V, transferrin, lactoferrin, albumins, and gelatine. All blood samples contained precursors of ASC (p-ASC) able to produce IgM binding to these antigens in frequencies above 0.03% of B cells. Most interestingly, a significant difference exists between rheumatoid arthritis (RA) patients and controls, concerning the relative frequencies of p-ASC able to produce monospecific or multireactive RF. Whereas most p-ASC(RF) in RA patients are monospecific (mean ratio 3.7), most p-ASC(RF) in healthy control persons are cross-reactive with at least one of five other antigens tested (mean ratio 0.2). The data suggest a disease-specific expansion of p-ASC committed to the production of monospecific rheumatoid factors.
Rudolphi
U
U
Clinical Research Unit, University of Freiburg, Germany.
Hohlbaum
A
A
Lang
B
B
Peter
H H
HH
Melchers
I
I
D000917:Antibody Formation; D000918:Antibody Specificity / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D002478:Cells, Cultured; D018834:Chaperonin 60; D003094:Collagen / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000276:immunology; D012217:Rheumatoid Factor / Q000276:immunology
D001323:Autoantibodies; D001426:Bacterial Proteins; D018834:Chaperonin 60; D006360:Heat-Shock Proteins; D007074:Immunoglobulin G; D003094:Collagen; D012217:Rheumatoid Factor