Game of clones: How measles remodels the B cell landscape

Abstract

B cell receptor sequencing sheds light on how measles cripples the immune system long after recovery from clinical disease (see related Research Articles by Petrova et al. and Mina et al.).

Fig. 1.. Measles-induced lymphopenia results in altered naïve and memory B cell receptor repertoires after lymphocyte number recovery.

Variable region exons of Ig heavy and light chains are assembled in early bone marrow–resident B lineage cells to produce a vast diversity of B cell receptor specificities (represented by multicolored bone marrow). Most of this agnostically generated immature Ig repertoire is counterselected through tolerance filtration steps (represented by a square patch of filter material), releasing a fraction of the initial immature Ig repertoire expressed on mature naïve B cells. Mature naïve B cells can be activated by infections and vaccines to undergo clonal selection, somatic Ig mutation, and IgH class switch recombination from initially expressed IgM/IgD to IgG, IgA, or IgE. After activation, some B cells specific for past infections persist as memory B cells. The memory B cell pool is a way that B cells retain memory of immune history (represented by colored arrows). Measles virus results in the destruction of immune cells, including naïve and memory B cells, leading to lymphopenia that abates weeks after infection. Ig repertoire sequencing (Ig-seq) studies by Petrova et al. show that both naïve Ig repertoires and memory Ig repertoires are altered. They argue that the recovered Ig repertoires retain immature Ig repertoire features. This is particularly the case for 2 of the 19 measles-infected participants (~10%), which had an Ig repertoire after measles infection with heavy usage of DH-proximal VH gene segments—a feature seen in early bone marrow B lineage cells. This may suggest a transiently weakened Ig selection filter mechanism after measles in some individuals. In addition, the recovered memory B cells after measles infection somewhat paradoxically had a more diverse Ig repertoire compared with pre-measles.