The lambda gene immunoglobulin repertoire of human neonatal B cells.
The dynamics of immunoglobulin rearrangements and selection, which depend on age, antigen exposure and tolerance functions, are only partly understood. Thus, we analyzed and compared the lambda chain immunoglobulin repertoire of individual IgD+ human neonatal B cells with the adult peripheral B cell VlambdaJlambda repertoire. Some Vlambda genes, 4C, 2A2, 2B2, 5A, 1G and 4B, were overexpressed in the non-productive neonatal repertoire, whereas other Vlambda genes (2E, 2A2, 3H, 2B2, 1C and 1G) were overexpressed in the productive repertoire. The adult B cell repertoire revealed nearly the same predominance of genes in the non-productive and productive repertoire. A comparison of the non-productive and productive repertoire indicated that the genes 3H and 1C were positively selected, whereas the genes 4C, 2A1, 3I, 5A, 9A, 4A and 4B were negatively selected. All four functional Jlambda genes were used in both repertoires. Jlambda2/3 was used mainly. Insertions of non-templated nucleotides at the VlambdaJlambda-junction by the enzyme TdT were less frequent as compared to the adult, but the CDR3 length was the same. Comparison of CD5+IgD+ and CD5-IgD+ B cells revealed no differences between neonatal productive rearrangements. However, the genes 1C and 1G were used more often in the non-productive repertoire of CD5+ B cells, whereas gene 4B was used significantly more frequent in CD5- B cells. These data provide evidence that the primary usage and subsequent selection of Vlambda genes in the neonate are surprisingly comparable with the adult. This suggests that selection into the productive Vlambda repertoire in principal might be driven mainly by autoantigens in the newborn, as well as in adulthood, since newborns have not been exposed to exogenous antigens.
Children's Hospital, Pediatric Immunology, Rheumatology and Infections Diseases, University of Wuerzburg, Wuerzburg, Germany. Petra.Richl@uni-wuerzburg.de
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Richl
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Stern
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Lipsky
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HJ
Girschick
D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D018956:CD5 Antigens / Q000276:immunology; D022801:Complementarity Determining Regions / Q000235:genetics; D004252:DNA Mutational Analysis; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D005092:Exonucleases / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007072:Immunoglobulin D / Q000235:genetics; D007144:Immunoglobulin J-Chains / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D007231:Infant, Newborn
D018956:CD5 Antigens; D022801:Complementarity Determining Regions; D007072:Immunoglobulin D; D007144:Immunoglobulin J-Chains; D007146:Immunoglobulin lambda-Chains; D004253:DNA Nucleotidylexotransferase; D005092:Exonucleases