Contribution of light chain rearrangement in peripheral B cells to the generation of high-affinity antibodies.
Recently, peripheral B cells have been shown to undergo secondary V(D)J rearrangement of immunoglobulin genes, but the physiological role of this event has not been fully elucidated. To investigate whether rearrangement of L chain genes in the periphery is involved in the generation of high-affinity antibodies (Ab), we used the 17.2.25 rearranged VHDJH gene (VHT)-knockin mouse whose B cell diversity is limited due to the expression of the site-directed transgene. Immunization of the mouse with p-nitrophenylacetyl (pNP)-conjugated chicken gamma-globulin preferentially led to the production of anti-pNP IgG Ab comprised of non-VHT-encoded H chains and lambda chains. lambda(+) IgG constituted a majority of high-affinity Ab to this hapten. RAG-2 mRNA and the recombination signal sequence break of the lambda1 gene increased in the draining lymph node of immunized mice, but not of nonimmunized animals. There was a close correlation between the levels of these parameters implicating lambda gene rearrangement and the production of lambda(+ )high-affinity anti-pNP IgG. These observations were reproduced in RAG-1-deficient mice that were reconstituted with the spleen cells ofthe knockin mouse. Thus, our findings suggest that L chain rearrangement that occurs in the periphery can contribute to affinity maturation of Ab.
Magari
Masaki
M
Department of Biotechnology, Faculty of Engineering, Okayama University, Okayama, Japan.
Sawatari
Takashi
T
Kawano
Yohei
Y
Cascalho
Marilia
M
Wabl
Matthias
M
Kanayama
Naoki
N
Hikida
Masaki
M
Ohmori
Hitoshi
H
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000915:Antibody Affinity / Q000235:genetics*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001483:Base Sequence; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D007114:Immunization; D007074:Immunoglobulin G / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D020395:Receptors, Interleukin-7 / Q000037:antagonists & inhibitors; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013154:Spleen / Q000166:cytology / Q000276:immunology; D045567:VDJ Recombinases
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007146:Immunoglobulin lambda-Chains; D020395:Receptors, Interleukin-7; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases