期刊
JOURNAL OF IMMUNOLOGY
卷 181, 期 12, 页码 8409-8415出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.12.8409
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资金
- National Institutes of Health [AI07051, AI42732, AI48115, HD043327, TW02130]
- Deutsche Forschungsgemeinschaft [SFB/TR22-TPA17]
- Alexander von Humholdi-Stiftung [FLF1071957]
All jawed vertebrates limit use of D-H reading frames (RFs) that are enriched for hydrophobic amino acids. In BALB/c mice, DFL16.1 RF2 encodes valine and isoleucine. To test whether increased use of RF2 affects B cell function, we examined B cell development and Ab production in mice with an IgH allele (Delta D-D mu FS) limited to use of a single, frameshifted DFL61.1 gene segment. We compared the results of these studies to wild-type mice, as well as those previously obtained in mice limited to use of either a single normal D-H or a single inverted D-H that forces use of arginine in CDR-H3. All three of the mouse strains limited to a single D-H produced fewer immature B cells than wild type. However, whereas mice limited to a single normal D-H achieved normal B cell numbers in the periphery, mice forced to preferentially use RF2 had reduced numbers of mature B cells in the spleen and bone marrow, mirroring the pattern previously observed in mice enriched for charged CDR-H3s. There were two exceptions. B cells in the mice using RF2 normally populated the marginal zone and peritoneal cavity, whereas mice using inverted RF1 had increased numbers of marginal zone B cells and decreased numbers of B1a cells. When challenged with several T-dependent or T-independent Ags, Ag-specific Ab titers in the mice forced to use RF2 were altered. These findings indicate that B cell development and Ag-specific Ab production can be heavily influenced by the global amino acid content of the CDR-H3 repertoire. The Journal of Immunology, 2008, 181: 8409-8415.
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