Somatic mutation of immunoglobulin V genes in vitro.
The molecular mechanism behind affinity maturation is the introduction of point mutations in immunoglobulin (Ig) V genes, followed by the selective proliferation of B cells expressing mutants with increased affinity for antigen. An in vitro culture system was developed in which somatic hypermutation of Ig V genes was sustained in primed B cells. Cognate T cell help and cross-linking of the surface Ig were required, whereas the addition of lipopolysaccharide or a CD40 ligand to drive proliferation was insufficient. This system should facilitate understanding of the molecular and cellular mechanisms that regulate somatic mutation and B cell selection.
Källberg
E
E
Immunology Unit, Lund University, Sweden.
Jainandunsing
S
S
Gray
D
D
Leanderson
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D019013:CD40 Antigens; D023201:CD40 Ligand; D002478:Cells, Cultured; D018920:Coculture Techniques; D005803:Genes, Immunoglobulin; D006241:Haptens / Q000276:immunology; D006825:Hybridomas; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D010047:Ovalbumin / Q000276:immunology; D010081:Oxazolone / Q000031:analogs & derivatives / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014162:Transfection
D019013:CD40 Antigens; D006241:Haptens; D007135:Immunoglobulin Variable Region; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; C018361:2-phenyloxazolone; D023201:CD40 Ligand; D010081:Oxazolone; D010047:Ovalbumin