title: Recirculating bone marrow B cells in C57BL/6 mice are more tolerant of highly hydrophobic and highly charged CDR-H3s than those in BALB/c mice.
abstract: To test whether mechanisms controlling the range of diversity of the developing antibody repertoire in C57BL/6 mice (IgH(b)) operate similarly to those identified in BALB/c mice (IgH(a)), we compared the sequences of VH 7183-containing H-chain transcripts from sorted adult bone marrow C57BL/6 B-cell subsets with those previously obtained from BALB/c mice. Patterns of VDJ gene segment utilization and CDR-H3 amino acid composition, charge, and average length in C57BL/6 pro-B cells were similar, although not identical, to BALB/c pro-B cells. However, C57BL/6 mature, recirculating B cells failed to demonstrate the reduction in the use of VH81X and the narrowing in the range of variance of CDR-H3 hydrophobicity that characterizes B-cell maturation in BALB/c mice. To further test the ability of the C57BL/6 strain to discard B cells expressing highly charged CDR-H3s, we introduced a mutant IgH(a) DH allele that forces use of arginine, asparagine, and histidine. Unlike BALB/c mice, C57BL/6 mice congenic for the charged DH maintained normal numbers of mature, recirculating B cells that were enriched for charged CDR-H3s. Together these findings indicate that the mature C57BL/6 B-cell pool permits expression of immunoglobulins with antigen-binding sites that are typically discarded during late-stage bone marrow B-cell development in BALB/c mice.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Khass
authors.forename: Kevin
authors.initials: K
authors.lastname: Buckley
authors.forename: Pratibha
authors.initials: P
authors.lastname: Kapoor
authors.forename: Robert L
authors.initials: RL
authors.lastname: Schelonka
authors.forename: Leticia S
authors.initials: LS
authors.lastname: Watkins
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Harry W
authors.initials: HW
authors.lastname: Schroeder
mesh_terms: D000818:Animals; D000916:Antibody Diversity / Q000235:genetics / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003062:Codon; D022801:Complementarity Determining Regions / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000276:immunology; D057927:Hydrophobic and Hydrophilic Interactions; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016364:Reading Frames
chemical_list: D003062:Codon; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains