TY - JOUR
T1 - Preferential use of DH reading frame 2 alters B cell development and antigen-specific antibody production
AU - Schelonka, Robert L.
AU - Zemlin, Michael
AU - Kobayashi, Ryoki
AU - Ippolito, Gregory C.
AU - Zhuang, Yingxin
AU - Gartland, G. Larry
AU - Szalai, Alex
AU - Fujihashi, Kohtaro
AU - Rajewsky, Klaus
AU - Schroeder, Harry W.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2008/12/15
Y1 - 2008/12/15
N2 - All jawed vertebrates limit use of DH 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 (ΔD-DμFS) 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 DH or a single inverted DH that forces use of arginine in CDR-H3. All three of the mouse strains limited to a single DH produced fewer immature B cells than wild type. However, whereas mice limited to a single normal DH 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.
AB - All jawed vertebrates limit use of DH 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 (ΔD-DμFS) 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 DH or a single inverted DH that forces use of arginine in CDR-H3. All three of the mouse strains limited to a single DH produced fewer immature B cells than wild type. However, whereas mice limited to a single normal DH 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.
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U2 - 10.4049/jimmunol.181.12.8409
DO - 10.4049/jimmunol.181.12.8409
M3 - Article
C2 - 19050258
AN - SCOPUS:58849120982
SN - 0022-1767
VL - 181
SP - 8409
EP - 8415
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -