Germinal centres articles from across Nature Portfolio

B cell activation in the germinal centre (GC) is accompanied by metabolic adaptation, but the functions of mitochondria remodelling during this process is unclear. Here the authors find that B cell-specific deficiency of Tfam, a transcription factor modulating mitochondria remodelling, impacts GC responses and induces aged immune features in B cells.

Bob1 manages ICOS and cellular respiration in Tfh cells, ensuring the sustained generation of specific humoral responses. This likely contributes to persistent inflammation resulting from recurring allergen exposure.

Calmodulin-dependent kinase 4 (CaMK4) has been implicated in humoral immunity. Here, the authors demonstrate that CaMK4 expression controls the differentiation of T follicular helper cells, leading to the expansion of pathogenic B cells in systemic lupus erythematosus.

Protein antigens, such as HIV envelope protein, require adjuvants for high immunogenicity. Here the authors show that a combined adjuvant approach with slow antigen delivery and potent ISCOMs adjuvant primes robust germinal center activity and humoral immunity in non-human primates. pSer-modified antigen shifts immunodominance to allow subdominant epitope-targeting of rare B cells.

Loss-of-function mutations in the chromatin remodelling protein HELLS result in humoral immune deficiency. Authors here show in a conditional knockout mouse model that HELLS controls the kinetics of a typical germinal center response by DNA methylation, its absence leading to either the appearance of memory-B cell markers or a metabolic state change typical of plasma cells.

Re-exposure to a previously encountered antigen leads to robust antibody responses and the formation of ‘recall’ germinal centres. A preprint by Schiepers et al. shows that antibody feedback in these germinal centres ensures the maturation of naive B cells that can target escape epitopes.

Susceptibility to respiratory pathogens is increased during early life, yet children can mount highly effective immune responses to novel pathogens in the absence of a fully developed immune system. We found that bronchus-associated lymphoid tissue (BALT) develops in the lungs early in life and supports germinal center formation and B cell differentiation to produce antibodies specific for respiratory pathogens, revealing a mechanism for immune protection in an as-yet-undeveloped immune system.

Naive B cells activated during infection enter the germinal center (GC) reaction, in which high-affinity antibodies are generated. A new study has uncovered a distinct metabolic requirement for B cells poised to undergo the GC reaction, whose activation required lactate dehydrogenase A-dependent aerobic glycolysis.

The magnitude and quality of the germinal center response after vaccination decline with age. We found that T follicular helper (T_FH) cells are enriched in the dark zone of germinal centers in aged mice, which impairs the expansion of the follicular dendritic cell network upon immunization and reduces antibody responses.