Lineage tree analysis of high throughput immunoglobulin sequencing clarifies B cell maturation pathways

Abstract

In this study, we used lineage tree analysis of Ig heavy chain gene sequences from five human B cell subsets (TR, NA, MM, SM and DN) from three individuals, to study the relationships between these B cell populations and garner insights regarding their roles in immune responses. Our analyses confirmed that both MM and SM branches can include DN Ig sequences, sometimes identical to SM Ig sequences. MM trees were significantly shorter than SM trees. Even when they belonged to the same clone, MM branches were shorter, consistent with either an early exit of MM cells from germinal centers in a T-dependent response, before accumulating many mutations, or their generation by Tindependent responses. Our finding of combined trees that included both MM and SM sequences suggests that at least some MM cells originate from the same clones as SM, rather than develop separately.