Longitudinal monitoring of class-switched memory-B cell proportions identifies plausible germinal center failure in patients with suspected immune disorders.

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A reduced proportion of peripheral class-switched memory B cells (CSM-B cells) is presumed to indicate ineffective germinal activity. The extent that this finding corresponds to a plausible germinal center failure pathophysiology in patients not diagnosed with CVID or hyper IgM syndrome is not known. We asked if patients with low CSM-B cells are more likely to demonstrate failure to produce serum IgA and IgG than counterparts with nonreduced class-switched memory B cell levels, regardless of diagnosis. Patients with low CSM-B cell levels regardless of diagnosis were retrospectively compared with their counterparts without CSM-B cell reductions for demographics and serum immunoglobulin levels. Patients were further divided based on whether CSM-B cell levels remained low over time or fluctuated, and these groups were compared for serum immunoglobulin levels and diagnoses. Of 305 patients, those with CSM-B cell (n = 50) reductions were more likely to have low serum IgA and IgG than those without reductions. Of the 78 patients in whom CSM-B cells were measured repeatedly over time, 21 patients had low CSM-B cell levels, but this finding was persistent in only 10. Patients with persistent CSM-B cell reductions universally had severe serum IgA and IgG deficiencies and patients with transient CSM-B cell reduction often did not. These two groups contained divergent diagnoses and likely represent separate pathophysiologic groups. Quantifying CSM-B cells as a percentage of CD27+ B cells repeatedly over time is a robust approach to identifying patients with a plausible germinal center failure endotype.