Persistent expression of an unproductive immunoglobulin heavy chain allele with DH-JH-gamma configuration in peripheral tissues.
Genomic recombination events, including VDJ recombination (VDJR) and class-switch recombination (CSR), are indispensable for the adaptation and progression of the acquired immune system. These processes are completed by orderly, temporal onsets of the gene rearrangements along with B-cell differentiation. The presence of various premature transcripts of immunoglobulin heavy chain (IgH) alleles has been demonstrated during B-cell ontogeny. These include D(H)-J(H) (DJ)-mu, J(H)-mu, and sterile transcripts of C(H). Since these transcripts can be detected during the onset of VDJR and CSR, their presence is believed to reflect a structural change in the genome, favoring VDJR and CSR. This report presents evidence of persistent DJ transcription and onset of CSR on an unproductive IgH allele in peripheral tissues. Nucleotide sequence analysis revealed that these transcripts showed DJ-gamma (Dgamma) configuration and that characteristics of the variable region were essentially the same as those of the DJ-mu transcript previously described. It was noted that the small intestine abundantly expresses Dgamma transcripts with gamma2b and gamma1 isotypes of the IgH constant region. The present findings indicate the onset of CSR preceding V(H) to DJ joining in an unproductive IgH allele of the peripheral B cell and the specificity for the gut-associated condition for B-cell differentiation in the small intestine.
Ono
Masao
M
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. onomasao@mail.tains.tohoku.ac.jp
Nose
Masato
M
D000483:Alleles; D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001483:Base Sequence; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000276:immunology; D018928:Immunity, Mucosal; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region