A new perspective is needed for positive selection of germinal center B cells with higher-affinity B cell receptors

In a recent issue of Nature Immunology,Chen et al.identified differential expression signatures of metabolic programs within the germinal center(GC)compartment to distinguish GC B cells from different zones[1].Furthermore,they identified an important role of oxidative phosphorylation(OXPHOS)in the process of positive selection of B cells with higher-affinity B cell receptors(BCRs)in GCs.GCs are inducible secondary lymphoid microanatomical structures that provide niches for B cells to capture and present antigens in the light zone(LZ)and to undergo clonal expansion and BCR somatic hypermutation(SHM)in the dark zone(DZ)Fig.1.Alternating migration of activated GC B cells between the LZ and DZ is assumed to result in positive selection of clones with higher-affinity B cell antigen receptors.These clones are characterized by accelerated cell division,suggesting a genomic program activated by BCR and CD40 signaling[2].