Experimental Animal Division

Memory B cells are long-lived quiescent B cells selected for their expression of somatically mutated, high-affinity antibodies in the T cell-dependent germinal center (GC) reaction. This reaction is accompanied by the up-regulation of the transcriptional repressor B cell leukemia/lymphoma 6 (Bcl6), on which GC B cell differentiation depends. A puzzling observation has been that the memory B cell compartment also contains cells expressing unmutated, low-affinity antibodies. To obtain a comprehensive understanding of the population dynamics underlying GC-dependent and -independent memory B cell development, Takemori and colleagues established a mutant mouse strain carrying aloxP-flanked Bcl6 exons 7-9 allele, with these exons encoding the Bcl6 zinc finger domains ZF1 to ZF5. Using conditional Bcl6 ablation, they demonstrated that the unmutated memory cells are generated through proliferative expansion early after immunization in a T cell-dependent, GC-independent manner. GC-independent memory B cells are joined later by their somatically mutated GC descendants, and both types of memory cells efficiently generate an adoptive secondary antibody response [1].