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

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Abstract
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 bavis (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 003% 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 multircactive 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.