Heterogeneous RF structures between and within healthy individuals are not related to HLA DRB1 ∗0401

Abstract

To study variations in Rheumatoid Factor (RF) autoantibodies between and within healthy individuals, we have produced and analysed the variable heavy chain (V H) regions of 18 new monoclonal IgM RFs from the peripheral blood of two healthy subjects before and after immunization with tetanus toxoid (TT). The majority of these RFs used germline genes of the V H3 family, but RFs of the V H1, V H2 and V H7 families were also found. No RF of the V H4 RF is found. Fourteen different V H germline (GL) genes encoded the RFs, suggesting an extraordinary heterogeneity in structure. Consequently, changes in RF V region structures following immunization were difficult to identify. There were, however, structural differences between RFs from the two donors. RFs from one donor (IP) used more λ light chains than RFs from the other donor and previously described RFs. In addition, 50% of the RFs from donor IP were encoded by GL genes frequently found to encode RFs from patients with Rheumatoid Arthritis (RA) but not described in RFs from other healthy subjects. The predominant use of V H3 RFs in the two healthy donors contrasts with the over-expression and expansion of V H1 RFs in one previously described healthy immunized donor. There are thus large individual differences in RF structures, which might be related to the immunological status, environment or genetic background of the donors. However, since these three donors are all HLA DRB1 ∗0401, it is unlikely that this HLA type, associated with seropositive RA, accounts for the individual differences.