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MRL/lpr mice with a knock‐in BCR show much less efficient receptor‐editing to membrane‐bound antigen
Author(s) -
Carey John,
Lamoureux Jennifer,
Feeney Ann
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.669.18
Subject(s) - antigen , microbiology and biotechnology , breakpoint cluster region , cd19 , receptor , b cell receptor , biology , immunoglobulin light chain , t cell receptor , b cell , downregulation and upregulation , chemistry , immunology , antibody , t cell , gene , genetics , immune system
Receptor editing is the main mechanism by which self‐reactive BCR are removed in immature B cells. Using 3‐83 BCR transgenic mice on the MRL/lpr and B10 background, we have previously shown that receptor editing is less efficient in MRL/lpr mice using indirect measures of receptor editing such as RAG upregulation. Now we have bred the 3‐83 gene‐targeted heavy and light chain genes onto the MRL/lpr background, on both the antigenic H‐2 k and non‐antigenic H‐2 d background. These mice can therefore undergo normal receptor editing since the targeted light chain is in the kappa locus. Unlike the B10 3‐83 knock‐in mice, where the B cell number is similar whether self antigen (H‐2 k ) is present or not, we find that the spleens of MRL/lpr knock‐in mice have greatly reduced B cell numbers if self‐antigen is present. Furthermore, the level of CD19 is greatly reduced in the presence of antigen. Finally, B10 mice increase their marginal zone compartment in the presence of antigen, while MRL/lpr mice lose the MZ compartment. Thus, in the MRL/lpr mice, clonal deletion appears to be the main mechanism of eliminating B cells reactive to membrane bound antigen, while in the B10 non‐autoimmune mice, receptor editing efficiently makes a non‐self reactive normal B cell repertoire.