MODULATION AND HIGH-FREQUENCY EXPRESSION OF AUTOANTIBODY-ASSOCIATED CROSS-REACTIVE IDIOTYPES LINKED TO THE V(H)I-SUBGROUP IN CD5-EXPRESSINGB-LYMPHOCYTES FROM PATIENTS WITH CHRONIC LYMPHOCYTIC-LEUKEMIA (B-CLL)

Leukaemic B cells from patients with chronic lymphocytic leukaemia (B- CLL) are known to express the pan T-cell marker CD5 and a restricted s et of immunoglobulin (Ig) variable region heavy (V(H)) and light (V(L) ) chains encoded by germline or minimally mutated germline genes. We h ave studied surface expression of certain V(H) and V(K) gene products on peripheral blood B lymphocytes from 23 patients with B-CLL, using a panel of monoclonal antibodies (MoAbs) recognizing germline encoded c ross-reactive idiotypes (CRI) associated with V(H)I (G6, G8), V(H)III (B6, D12), V(K)IIIb (17-109) and an epitope linked to the V(K)III ligh t chain subgroup (C7). While only 1.7-3.2% of peripheral blood B lymph ocytes from normal individuals expressed the V(H)I-associated CRI (V(H )I-CRI), these CRI were expressed on virtually all the leukaemic B cel ls from 17-22% of the CLL patients. The V(H)III-associated CRI (V(H)II I-CRI), however, were found in 8.5-13% of the CLL B cells. Fifty per c ent of the IgMK-expressing CLL cells (7/14) expressed the V(K)III ligh t chain subgroup of which only one expressed the V(K)IIIb-associated C RI (V(K)IIIb-CRI), 17-109. The anti-V(H)I-associated CRI antibodies we re used to study their regulatory effect on in vitro Ig synthesis by t he leukaemic cells. A significant suppression of spontaneous and mitog en-driven Ig production was observed in all cases studied. These resul ts demonstrate an over-expression of V(H)I and V(K)III gene products i n B-CLL and suggest that B cells expressing these CRI are particularly susceptible to lymphoproliferative stimuli. The anti-CRI antibodies c an be used to modulate Ig production by the leukaemic cells and may be of potential value for selective immunotherapy.