HnRNPK restrains memory precursor and plasma cell differentiation to control germinal center B-cell output.

HnRNPK deficiency in germinal center B cells markedly increases plasma cell differentiation and reduces germinal center B-cell numbers by up to 50%.

• Why it matters: Understanding the transcriptional and metabolic regulation of B-cell fate decisions is crucial for insights into antibody production and immune memory, yet these mechanisms are not well characterized.
• What they did: Researchers generated mice with B and GC B-cell-specific knockout of hnRNPK, revealing that its deletion impairs B-cell development and significantly attenuates the GC B-cell response, with increased precursor differentiation.
• The result: HnRNPK suppresses plasma cell differentiation by transcriptionally repressing Hhex and Zfp318 and modulating glycolysis and CD25 expression; blocking IL-2/CD25 signaling rescues GC defects, highlighting potential therapeutic targets.