TY - JOUR
T1 - DH and JH usage in murine fetal liver mirrors that of human fetal liver
AU - Schelonka, Robert L.
AU - Szymanska, Ewa
AU - Vale, Andre M.
AU - Zhuang, Yingxin
AU - Gartland, G. Larry
AU - Schroeder, Harry W.
N1 - Funding Information:
Acknowledgements The authors wish to thank P. Burrows, M. Cooper, J. Kearney, and R. F. Maier for their invaluable advice and support. This work was supported in part by AI07051, AI42732, AI48115, AI078449, T32 AI07051, HD043327, Deutsche For-schungsgemeinschaft SFB/TR22-TPA17, and Alexander von Humboldt-Stiftung FLF1071857. The authors declare that they have no competing financial interests.
Funding Information:
This work was supported in part by AI07051, AI42732, AI48115, AI078449, HD043327, Deutsche Forschungsgemeinschaft SFB/ TR22-TPA17, and Alexander von Humboldt-Stiftung FLF1071857. The authors declare that they have no competing financial interests.
PY - 2010/10
Y1 - 2010/10
N2 - In mouse and human, the regulated development of antibody repertoire diversity during ontogeny proceeds in parallel with the development of the ability to generate antibodies to an array of specific antigens. Compared to adult, the human fetal antibody repertoire limits N addition and uses specifically positioned VDJ gene segments more frequently, including V6-1 the most DH-proximal VH, DQ52, the most JH-proximal DH, and JH2, which is DH-proximal. The murine fetal antibody repertoire also limits the incorporation of N nucleotides and uses its most DH proximal VH, VH81X, more frequently. To test whether DH and JH also follow the pattern observed in human, we used the scheme of Hardy to sort B lineage cells from BALB/c fetal and neonatal liver, RT-PCR cloned and sequenced V H7183-containing VDJCμ transcripts, and then assessed V H7183-DH-JH and complementary determining region 3 of the immunoglobulin heavy chain (CDR-H3) content in comparison to the previously studied adult BALB/c mouse repertoire. Due to the deficiency in N nucleotide addition, perinatal CDR-H3s manifested a distinct pattern of amino acid usage and predicted loop structures. As in the case of adult bone marrow, we observed a focusing of CDR-H3 length and CDR-H3 loop hydrophobicity, especially in the transition from the early to late pre-B cell stage, a developmental checkpoint associated with expression of the pre-B cell receptor. However, fetal liver usage of JH-proximal DHQ52 and D H-proximal JH2 was markedly greater than that of adult bone marrow. Thus, the early pattern of DH and JH usage in mouse feta liver mirrors that of human.
AB - In mouse and human, the regulated development of antibody repertoire diversity during ontogeny proceeds in parallel with the development of the ability to generate antibodies to an array of specific antigens. Compared to adult, the human fetal antibody repertoire limits N addition and uses specifically positioned VDJ gene segments more frequently, including V6-1 the most DH-proximal VH, DQ52, the most JH-proximal DH, and JH2, which is DH-proximal. The murine fetal antibody repertoire also limits the incorporation of N nucleotides and uses its most DH proximal VH, VH81X, more frequently. To test whether DH and JH also follow the pattern observed in human, we used the scheme of Hardy to sort B lineage cells from BALB/c fetal and neonatal liver, RT-PCR cloned and sequenced V H7183-containing VDJCμ transcripts, and then assessed V H7183-DH-JH and complementary determining region 3 of the immunoglobulin heavy chain (CDR-H3) content in comparison to the previously studied adult BALB/c mouse repertoire. Due to the deficiency in N nucleotide addition, perinatal CDR-H3s manifested a distinct pattern of amino acid usage and predicted loop structures. As in the case of adult bone marrow, we observed a focusing of CDR-H3 length and CDR-H3 loop hydrophobicity, especially in the transition from the early to late pre-B cell stage, a developmental checkpoint associated with expression of the pre-B cell receptor. However, fetal liver usage of JH-proximal DHQ52 and D H-proximal JH2 was markedly greater than that of adult bone marrow. Thus, the early pattern of DH and JH usage in mouse feta liver mirrors that of human.
KW - Adult mouse repertoire
KW - CDR-H3
KW - Fetal mouse repertoire
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U2 - 10.1007/s00251-010-0469-5
DO - 10.1007/s00251-010-0469-5
M3 - Article
C2 - 20714894
AN - SCOPUS:77957571907
SN - 0093-7711
VL - 62
SP - 653
EP - 666
JO - Immunogenetics
JF - Immunogenetics
IS - 10
ER -