B cell receptor signal strength determines B cell fate

• DOI: 10.1038/ni1036
• Publication Date: 2004-02-02T16:53:57Z
• Authors: Stefano Casola; Kevin L Otipoby; Marat Alimzhanov; Sibille Humme; Nathalie Uyttersprot; Jeffery L Kutok; Michael C Carroll; Klaus Rajewsky
• Keywords: breakpoint cluster region; Cell fate determination; Naive B cell

B cell receptor (BCR)-mediated antigen recognition is thought to regulate B cell differentiation. BCR signal strength may also influence B cell fate decisions. Here, we used the Epstein-Barr virus protein LMP2A as a constitutively active BCR surrogate to study the contribution of BCR signal strength in B cell differentiation. Mice carrying a targeted replacement of Igh by LMP2A leading to high or low expression of the LMP2A protein developed B-1 or follicular and marginal zone B cells, respectively. These data indicate that BCR signal strength, rather than antigen specificity, determines mature B cell fate. Furthermore, spontaneous germinal centers developed in gut-associated lymphoid tissue of LMP2A mice, indicating that microbial antigens can promote germinal centers independently of BCR-mediated antigen recognition.