Induction of somatic hypermutation by antigen-specific B cell receptors in the human BL2 cell line.
The role of the B cell antigen receptor in the induction of somatic hypermutation is presently unclear. We established stable transfectants of the human BL2 cell line expressing hen-egg lysozyme-specific IgM or IgA and compared their ability to induce somatic hypermutation of the endogenous rearranged heavy-chain gene. We found that IgM and IgA were both able to induce somatic hypermutation in an antigen dose-independent manner. The mutations displayed most of the characteristics of somatic hypermutation in vivo. Notably, some replacements introduced stop codons in the coding region. Our data suggest that class-switched memory B cells may undergo somatic hypermutation. They also suggest that the transmembrane/cytoplasmic domains of the class-switched isotypes modulate the signaling and down-modulation activities of the BCR in an antigen dose-dependent manner.
Glaudet
Florence
F
CNRS UMR 6101, Laboratoire d'Immunologie, Faculté de Médecine, Limoges, France.
Denis
Vincent
V
Cogné
Michel
M
Khamlichi
Ahmed Amine
AA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics / Q000276:immunology*; D005803:Genes, Immunoglobulin / Q000235:genetics / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009113:Muramidase / Q000276:immunology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics / Q000276:immunology*; D014162:Transfection
D007132:Immunoglobulin Isotypes; D011947:Receptors, Antigen, B-Cell; D012313:RNA; C421864:hen egg lysozyme; D009113:Muramidase