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 experimental allergic encephalomyelitis (EAE) in a variety of animal species, including rats and mice. We have previously described the ability of the newly described mouse lambda (lambda) variable (V) region V lambda x, to confer MBP reactivity to an Ab. In this report, we have evaluated the heavy (H) chain isotype distribution of V lambda x-bearing Abs in normal mouse serum. We demonstrate a biased H chain isotype association with V lambda x light (L) chains with a skewing towards gamma 2a and 2b isotypes. The IgG2a restriction in normal mouse Igs is even more evident in V lambda x-containing Abs that bind MBP. This was confirmed 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 encompassing residues 25-34 of the MBP molecule. Furthermore, virtually all of the reactivity of V lambda x-containing Abs with MBP peptide 25-34 is associated with the gamma 2a isotype. Collectively, these results suggest that the interaction of V lambda x with MBP seems to be facilitated by an association with gamma 2a which may reflect preferred VH usage by this isotype. Such unique pairing of particular H chains with V lambda x L chains in Abs that bind MBP may be indicative of a new B-cell component involved in the pathogenesis of EAE.
Galin
F S
FS
Department of Physiology and Biophysics, University of Alabama at Birmingham 35294, USA.
Zhou
S R
SR
Whitaker
J N
JN
Blalock
J E
JE
D000818:Animals; D000910:Antibodies, Heterophile / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D000937:Antigen-Antibody Reactions; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000032:analysis*; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000032:analysis*; D007146:Immunoglobulin lambda-Chains / Q000032:analysis*; D051379:Mice / Q000276:immunology*; D008807:Mice, Inbred BALB C; D004676:Myelin Basic Protein / Q000276:immunology* / Q000378:metabolism; D011817:Rabbits; D013045:Species Specificity
D000910:Antibodies, Heterophile; D000939:Epitopes; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains; D004676:Myelin Basic Protein