PREFERENTIAL ASSOCIATION OF V-LAMBDA-X LIGHT-CHAINS WITH GAMMA-2A HEAVY-CHAINS IN NATURALLY-OCCURRING HUMAN MYELIN BASIC-PROTEIN REACTIVE ANTIBODIES

Active immunization with myelin basic protein (MBP) induces experiment al allel gic encephalomyelitis (EAE) in a variety of animal species, i ncluding rats and mice. We have previously described the ability of th e newly described mouse lambda (lambda) variable (V) region, V lambda x, to confer MBP reactivity to an Ab, In this report, we have evaluate d the heavy (H) chain isotype distribution of V lambda x-bearing Abs i n normal mouse serum. We demonstrate a biased H chain isotype associat ion with V lambda x light (L) chains with a skewing towards gamma 2a a nd 2b isotypes. The IgG2a restriction in normal mouse Igs is even more evident in V lambda x-containing Abs that bind MBP. This was confirme d by the ability of purified polyclonal IgG2a Abs to bind MBP and the finding that most or all of the IgG2a Abs that bind MBP seem to harbor a V lambda x L chain. The specificity of naturally-occurring V lambda x-bearing Abs with MBP can be localized to a particular epitope encom passing residues 25-34 of the MBP molecule. Furthermore, virtually all of the reactivity of Vh x-containing Abs with MBP peptide 25-34 is as sociated with the gamma 2a isotype. Collectively, these results sugges t that the interaction of V lambda x with MBP seems to be facilitated by an association with gamma 2a which may reflect preferred V-H usage by this isotype. Such unique pairing of particular H chains with V lam bda x L chains in Abs that bind MBP may be indicative of a new B-cell component involved in the pathogenesis of EAE.