Somatic mutations in the variable region of the lambda 2 chain of M315 suppression of antibodies to the idiotype of M315.

Abstract

BALB/c mice immunized with purified BALB/c myeloma protein M315 (alpha, lambda 2) produce anti-idiotypic antibody directed predominantly to a combinational (VH-315 + VL-315) determinant(s) of the M315 paratope (Sirisinha and Eisen, 1971; Tungkanak and Sirisinha, 1976). We examined whether the unique B cell response is influenced by pretreatment of mice with fragments or chains derived from M315 before immunization with M315. Intravenous (i.v.) injection of the Fv-315 fragment (VH-315 + VL-315) into normal BALB/c mice seven days before immunization with M315 resulted in marked suppression of anti-M315 idiotype antibodies. Studies on the structural requirement for suppression indicated that VL-315, but not VH-315, is involved. Structural comparison with a defined lambda 2 light (L) chain suggested that three contiguous amino acid residues in the third hypervariable loop of the variable (V) domain of the L chain of M315 are important for down-regulation of production of antibodies to the M315 idiotype.