Determining the diversity of the naive B cell repertoire in African (Kenyan) population

The available reference databases for human immunoglobulin genes are largely based on alleles identified in Caucasian populations, which may not fully capture the allelic diversity of the global community. This limits B-cell analyses, as the accuracy of gene segment identification is dependent on the completeness of such reference databases.

In this study Sein and his team aim to characterise the overall naïve B cell repertoire in the African population. This will contribute towards providing information on region-specific allelic variants of immunoglobulins, thus improving the relevance of universal databases in an African setting. In addition, this work will create a reference baseline on the immunoglobulin gene usage in the naïve B cell repertoire within the African population for prospective germline targeting clinical trials and inform differences in immune responses observed.

Sein’s hypothesis is that the underlying continuous exposure to co-morbidity and immune activation that is prevalent in Africa shapes the composition of the naïve repertoire. Sub-Saharan Africa is known to bear the biggest burden of infectious diseases and the presence of persistent pathogens such as helminths, bacteria, parasites and viruses is common in a large proportion of its population. Malaria parasite offers one distinct pathogen that individuals on the continent are likely to be exposed to. In this study he will use varying historic malaria exposure to determine if comorbidity/ environmental immunomodulation impacts on shaping the naïve B cell repertoire.

This constant exposure raises the possibility that the cumulative effect of multiple and diverse ongoing or historical infections has a substantial role in shaping immunity.

SANTHE is an Africa Health Research Institute (AHRI) flagship programme funded by the Science for Africa Foundation through the DELTAS Africa programme; the Bill & Melinda Gates Foundation; Gilead Sciences Inc.; and the Ragon Institute of Mass General, MIT, and Harvard.