Nature 403:672

Glynne, R., S. Akkaraju, J.I. Healy, J. Rayner, C.C. Goodnow, and D.H. Mack. 2000

In the study by Glynne et al., the authors have begun to address the question of what distinguishes tolerant from non-tolerant B-lymphocytes at the level of gene expression.

The authors have used a well-studied model of B cell tolerance where mice have been engineered to express both B-lymphocytes specific for antigen, hen egg lysozyme (HEL), and soluble HEL as a self-antigen ("double-transgenic mice"). These mice recognize HEL as self and do not make anti-HEL antibodies. Oligonucleotide expression arrays were used to identify genes that are differentially expressed in tolerant and non-tolerant B cells. In addition, genes expressed by non-tolerant B-lymphocytes following challenge with antigen were characterized.

Out of 6,500 genes screened, expression of 20 genes was upregulated and expression of 8 genes downregulated in tolerant B cells relative to naïve B cells. In particular, B-lymphocytes from tolerant, double transgenic mice failed to upregulate the transcription factor, LSIRF, the proto-oncogene, c-myc and an anti-apoptotic protein, A1, in response to in vivo antigen stimulation. This pattern of gene expression is consistent with previous data showing that activation of JNK and NFkB is blocked in tolerant cells.

This study begins to define the gene expression profile of a tolerant B cell. Which of the genes identified need to be expressed in order to make a B cell tolerant in the first place remains to be determined.