TY - JOUR
T1 - A single DH gene segment creates its own unique CDR-H3 repertoire and is sufficient for B cell development and immune function
AU - Schelonka, Robert L.
AU - Ivanov, Ivaylo I.
AU - Jung, David H.
AU - Ippolito, Gregory C.
AU - Nitschke, Lars
AU - Zhuang, Yingxin
AU - Gartland, G. Larry
AU - Pelkonen, Jukka
AU - Alt, Frederick W.
AU - Rajewsky, Klaus
AU - Schroeder, Harry W.
PY - 2005/11/15
Y1 - 2005/11/15
N2 - To test the contribution of individual D gene segments to B cell development and function, we used gene targeting to create mice that contain only DFL16.1 in the DH locus. We term this D-limited IgH allele ΔD-DFL. Although the absolute number of IgM+IgD- B cells in the bone marrow was decreased, homozygous ΔD-DFL BALB/c mice contained normal numbers of IgM+IgD+ B cells in bone marrow and spleen and normal numbers of B1a, B1b, and B2 cells in the peritoneal cavity. Bone marrow IgM+IgD+ B cells express a CDR-H3 repertoire similar in length and amino acid composition to the DFL16.1 subset of the wild-type BALB/c repertoire but divergent from sequences that do not contain DFL16.1. This similarity in content is the product of both germline bias and somatic selection, especially in the transition to the mature IgM +IgD+ stage of development. Serum Ig concentrations and the humoral immune response to a T-dependent Ag ([4-hydroxy-3-nitrophenyl]acetyl hapten) were nearly identical to wild-type littermate controls. A greater variance in the immune response to the T-independent Ag (α(1→3)- dextran) was observed in ΔD-DFL homozygotes, with half of the mice exhibiting levels below the range exhibited by controls. Although limited to a repertoire specific to DFL16.1, the presence of a single DH gene segment of normal sequence was sufficient for development of normal numbers of mature B cells and for robust humoral immune function.
AB - To test the contribution of individual D gene segments to B cell development and function, we used gene targeting to create mice that contain only DFL16.1 in the DH locus. We term this D-limited IgH allele ΔD-DFL. Although the absolute number of IgM+IgD- B cells in the bone marrow was decreased, homozygous ΔD-DFL BALB/c mice contained normal numbers of IgM+IgD+ B cells in bone marrow and spleen and normal numbers of B1a, B1b, and B2 cells in the peritoneal cavity. Bone marrow IgM+IgD+ B cells express a CDR-H3 repertoire similar in length and amino acid composition to the DFL16.1 subset of the wild-type BALB/c repertoire but divergent from sequences that do not contain DFL16.1. This similarity in content is the product of both germline bias and somatic selection, especially in the transition to the mature IgM +IgD+ stage of development. Serum Ig concentrations and the humoral immune response to a T-dependent Ag ([4-hydroxy-3-nitrophenyl]acetyl hapten) were nearly identical to wild-type littermate controls. A greater variance in the immune response to the T-independent Ag (α(1→3)- dextran) was observed in ΔD-DFL homozygotes, with half of the mice exhibiting levels below the range exhibited by controls. Although limited to a repertoire specific to DFL16.1, the presence of a single DH gene segment of normal sequence was sufficient for development of normal numbers of mature B cells and for robust humoral immune function.
UR - http://www.scopus.com/inward/record.url?scp=27744561374&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27744561374&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.175.10.6624
DO - 10.4049/jimmunol.175.10.6624
M3 - Article
C2 - 16272317
AN - SCOPUS:27744561374
SN - 0022-1767
VL - 175
SP - 6624
EP - 6632
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -