title: Sequential generation of antibody diversity during B-cell development.
abstract: It has become increasingly apparent that generation of and variation in antigen-combining sites of antibodies occurs sequentially during B-cell development. Allelic and isotypic exclusion mechanisms ensure that a B cell produces antibody molecules having a single kind of combining site. A major reason for evolution of mechanisms which result in asynchronous formation of functional H and L chain genes may be the need for allelic and isotypic exclusion; but this may not be the only advantage of asynchronous formation of H and L chain genes. The evolution of mechanisms causing nonjunctional somatic mutation late in B cell development - only after antigen exposure apparently - may result from the biological advantages of: (1) 'fine tuning' of the combining site; (2) a response to an anti-idiotype regulatory network, or (3) expanded memory.
mesh_terms: D000483:Alleles; D000916:Antibody Diversity; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D001666:Binding Sites, Antibody; D002454:Cell Differentiation; D004247:DNA / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D007126:Immunoglobulin Allotypes / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics*; D009154:Mutation; D014176:Protein Biosynthesis; D012313:RNA / Q000032:analysis; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D007126:Immunoglobulin Allotypes; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007136:Immunoglobulins; D012313:RNA; D004247:DNA