Restricted IgA repertoire in both B-1 and B-2 cell-derived gut plasmablasts.
Mucosal IgA is the most abundantly produced Ig upon colonization of the intestinal tract with commensal organisms in the majority of mammals. The repertoire of these IgA molecules is still largely unknown; a large amount of the mucosal IgA cannot be shown to react with the inducing microorganisms. Analysis of the repertoire of used H chain Ig (V(H)) genes by H-CDR3 spectrotyping, cloning, and sequencing of V(H) genes from murine intestinal IgA-producing plasma cells reveals a very restricted usage of V(H) genes and multiple clonally related sequences. The restricted usage of V(H) genes is a very consistent observation, and is observed for IgA plasma cells derived from B-1 or conventional B-2 cells from different mouse strains. Clonal patterns from all analyzed V(H) gene sequences show mainly independently acquired somatic mutations in contrast to the clonal evolution patterns often observed as a consequence of affinity maturation in germinal center reactions in peripheral lymphoid organs and Peyer's patches. Our data suggest a model of clonal expansion in which many mucosal IgA-producing B cells develop in the absence of affinity maturation. The affinity of most produced IgA might not be the most critical factor for its possible function to control the commensal organisms, but simply the abundance of large amounts of IgA that can bind with relatively unselected affinity to redundant epitopes on such organisms.
Stoel
Maaike
M
Department of Cell Biology, Section Histology and Immunology, University of Groningen, Faculty Medical Sciences, Groningen, The Netherlands.
Jiang
Han-Qing
HQ
van Diemen
Cleo C
CC
Bun
Judy C A M
JC
Dammers
Peter M
PM
Thurnheer
M Christine
MC
Kroese
Frans G M
FG
Cebra
John J
JJ
Bos
Nicolaas A
NA
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D003001:Cloning, Molecular; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027041:Somatic Hypermutation, Immunoglobulin; D013045:Species Specificity; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism
D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region