期刊
BLOOD
卷 111, 期 3, 页码 1396-1403出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-08-110106
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资金
- NIAID NIH HHS [AI-67891, R01 AI067891] Funding Source: Medline
Pre-B lymphocytes consist of 2 distinct cell populations: large pre-B and small pre-B. The large pre-B cells are newly generated pre-B cells that express pre-B-cell receptor (pre-BCR) on the surface and are highly proliferative; small pre-B cells are derived from large pre-B cells that have down-regulated pre-BCR and withdrawn from cell cycle. The molecular events that mediate the transition from cycling pre-B to small, resting pre-B have not been fully elucidated. Here, we show that interferon regulatory factors 4 and 8 (IRF4,8) suppress surrogate light chain expression and down-regulate pre-BCR in pre-B cells. Our studies further reveal that IRF4,8 induce the expression of lkaros and Aiolos in pre-B cells, and reconstitution of expression of either one is sufficient to suppress surrogate light chain expression and down-regulate pre-BCR in pre-B cells lacking IRF4,8. Interestingly, our results also indicate that pre-B cells undergo growth inhibition and cellcycle arrest in the presence of IRF4,8. Moreover, we provide evidence that lkaros and Aiolos are indispensable for the down-regulation of pre-BCR and the cellcycle withdrawal mediated by IRF4,8. Thus, IRF4,8 orchestrate the transition from large pre-B to small pre-B cells by inducing the expression of lkaros and Aiolos.
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