Selection of Ig mu heavy chains by complementarity-determining region 3 length and amino acid composition.
Although it is generally accepted that Ig heavy chains (HC) are selected at the pre-B cell receptor (pre-BCR) checkpoint, the characteristics of a functional HC and the role of pre-BCR assembly in their selection have remained elusive. We determined the characteristics of HCs that successfully passed the pre-BCR checkpoint by examining transcripts harboring V(H)81X and J(H)4 gene segments from J(H)(+/-) and lambda5(-/-)mice. V(H)81X-J(H)4-HC transcripts isolated from cells before or in the absence of pre-BCR assembly had no distinguishing complementarity-determining region 3 traits. In contrast, transcripts isolated subsequent to passage through the pre-BCR checkpoint had distinctive complementarity-determining regions 3 of nine amino acids in length (49%) and a histidine at position 1 (73%). Hence, our data define specific structural requirements for a functional HC, which is instrumental in shaping the diverse B cell repertoire.
Martin
Denise A
DA
Department of Immunology, University of Toronto, and Ontario Cancer Institute, Toronto, Canada.
Bradl
Harald
H
Collins
Tara J
TJ
Roth
Edith
E
Jäck
Hans-Martin
HM
Wu
Gillian E
GE
D000596:Amino Acids / Q000032:analysis* / Q000235:genetics; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D022801:Complementarity Determining Regions / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006639:Histidine / Q000032:analysis / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D008958:Models, Molecular; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000276:immunology*; D017434:Protein Structure, Tertiary; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000596:Amino Acids; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007148:Immunoglobulin mu-Chains; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D006639:Histidine