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Publication : Contribution of light chain rearrangement in peripheral B cells to the generation of high-affinity antibodies.

First Author  Magari M Year  2002
Journal  Eur J Immunol Volume  32
Issue  4 Pages  957-66
PubMed ID  11920561 Mgi Jnum  J:76000
Mgi Id  MGI:2178197 Doi  10.1002/1521-4141(200204)32:4<957::AID-IMMU957>3.0.CO;2-A
Citation  Magari M, et al. (2002) Contribution of light chain rearrangement in peripheral B cells to the generation of high-affinity antibodies. Eur J Immunol 32(4):957-66
abstractText  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.
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