Expression pattern of the most JH-proximal human VH gene segment (VH6) in the B cell and antibody repertoire suggests a role of VH6-encoded IgM antibodies in early ontogeny.
We have developed a mAb (JE-6) that recognizes an Id encoded by the most JH-proximal human VH gene segment (VH6) in or near germ-line configuration. This mAb was used to determine the frequency of Id JE6+ B cells in large collections of monoclonal EBV-transformed and short term B cell lines derived from fetal, neonatal, and adult lymphoid tissues. Moreover, we investigated the presence of Id JE-6+ Ig in sera from neonates and adults and determined the (auto)antigen binding properties of VH6-encoded IgM mAb. We detected a fivefold overrepresentation of VH6-expressing IgM producing B cells in fetal tissues, cord blood, and adult bone marrow relative to adult blood. In cord blood, but not in adult blood sera, germ-line VH6-encoded IgM molecules were readily detectable. IgM secreted by VH6-expressing B cell clones displayed highly conserved and virtually identical autoantigen binding properties, independent of the length and composition of the IgH chain CDR3 region and L chain isotype. Collectively, these results suggest that the VH6 gene and the antibodies it encodes play an important role in early human ontogeny.
Van Es
J H
JH
Department of Immunology, University Hospital Utrecht, The Netherlands.
Raaphorst
F M
FM
van Tol
M J
MJ
Meyling
F H
FH
Logtenberg
T
T
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000916:Antibody Diversity / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D001666:Binding Sites, Antibody; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D005803:Genes, Immunoglobulin / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics*; D007130:Immunoglobulin Idiotypes / Q000032:analysis; D007144:Immunoglobulin J-Chains / Q000096:biosynthesis / Q000235:genetics*; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics*; D007231:Infant, Newborn; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data
D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007144:Immunoglobulin J-Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region