Repertoire diversification in mice with an IgH-locus-targeted transgene for the rearranged VH domain of a physiologically selected anti-ssDNA antibody.

Abstract:

:To test the fate of developing B cells with autoreactive receptor components, we studied mice homozygous for a knock-in transgene coding the VH domain of an IgM ssDNA-binding antibody. The transgene has unmutated C57 BL/6 V gene segments. Homozygous knock-in mice developed normal numbers of spleen and bone marrow B cells and normal serum Ig concentrations, and had the same low level of serum anti-ssDNA antibody as non-transgenic mice. Mature B cells expressed the transgene, and it underwent mutation and class switching. In young knock-in animals, nearly all IgM and some IgG cDNA clones from bone marrow and spleen contained the transgene V(H)D(H)J(H), with few or no mutations. In many IgM clones from older animals, however, and many IgG clones from both young and old mice, VH domains were revised by productive replacement with a new V(H)D(H) segment. VL segments were diverse. Immunized homozygous knock-in mice produced serum antibodies to polysaccharide, nucleic acid and protein antigens. Monoclonal IgM and IgG antibodies to nucleic acids used either transgenic or revised VH domains; but all of 20 IgG monoclonal antibodies to thyroglobulin used revised VH domain genes. Thus, B cells expressing an autoreactive (ssDNA-binding) VH domain did progress through development and were precursors for cells producing IgM and IgG, but underwent extensive VH gene revision in diversification of antibody responses.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Li J,Geissal ED,Li W,Stollar BD

doi

10.1016/j.molimm.2005.01.010

subject

Has Abstract

pub_date

2005-08-01 00:00:00

pages

1475-84

issue

12

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(05)00024-6

journal_volume

42

pub_type

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