B cell fate mapping reveals their contribution to the memory immune response against helminths

Abstract

An estimated quarter of the human world population is infected with gastrointestinal helminths causing major socioeconomic problems in endemic countries. A better understanding of humoral immune responses against helminths is urgently needed to develop effective vaccination strategies. Here, we used a fate mapping (FM) approach to mark germinal center (GC) B cells and their developmental fates by induced expression of a fluorescent protein during infection of mice with the helminth Nippostrongylus brasiliensis. We could show that FM⁺ cells persist weeks after clearance of the primary infection mainly as CD80⁺CD73⁺PD-L2⁺ memory B cells. A secondary infection elicited expansion of helminth-specific memory B cells and plasma cells (PCs). Adoptive transfers and analysis of somatic mutations in immunoglobulin genes further revealed that FM⁺ B cells rapidly convert to PCs rather than participating again in a GC reaction. These results provide new insights in the population dynamics of the humoral immune response against helminths.

Keywords: fate mapping; germinal center; helminths; memory responses; plasma cells.