Reduced life span of anergic self-reactive B cells in a double-transgenic model.

• DOI: 10.1084/jem.179.1.125
• Publication Date: 2004-06-24T07:56:10Z
• Authors: D A Fulcher; A Basten
• Keywords: Immunoglobulin D

The life span of anergic self-reactive B cells was determined by 5-bromo-2'-deoxyuridine (BrdU) loading tolerant double-transgenic (Dbl-Tg) mice produced mating hen egg lysozyme (HEL)-transgenic with the corresponding immunoglobulin-transgenic (Ig-Tg) mice, which express anti-HEL IgM and IgD. from Dbl-Tg despite being exposed to soluble antigen throughout their development, are not deleted, but persist in an state. As a prelude studying these cells, BrdU administered nontransgenic mice; bone marrow, spleen, lymph nodes displayed distinct kinetic profiles based on reciprocal expression B220 isoform CD45 heat-stable (HSA). Thus, immature B220lo/HSAhi incorporated rapidly suggesting recent generation dividing precursors, whereas uptake expressing mature B220hi/HSAlo phenotype significantly slower, consistent longer span. Such gating allowed analysis be directed at stable cell population transgenic mice. Comparison Ig- indicated that were renewed much higher rate (50% renewal times 0.64 vs. 3.4 wk for total 1.2 5.0 B200hi/HSAlo Dbl- Ig-transgenic respectively). This difference even more marked when restricted HEL-binding had 50% time 3-4 d compared 4-5 non-HEL-binding cells. While proportion cycle, entry newly generated into spleen similar, numbers reduced It therefore concluded have markedly decreased periphery. According studies radiation chimeras reconstituting HEL-transgenic recipients different serum levels Ig-Tg associated state per se, concentration HEL important only attaining critical threshold necessary tolerance induction. rendered exposure self-antigen survive relatively short period once they reached peripheral lymphoid tissue fail enter long-lived compartment.(ABSTRACT TRUNCATED AT 400 WORDS)