Antibody Repertoire and Gene Expression Dynamics of Diverse Human B Cell States During Affinity Maturation
33 Pages Posted: 16 Jun 2020 Sneak Peek Status: Under ReviewMore...
In response to antigen challenge, B cells clonally expand, undergo selection and differentiate to produce mature B cell subsets and high affinity antibodies. However, the interplay between dynamic B cell states and their antibody-based selection is challenging to decipher in primary human tissue. We have applied an integrated analysis of bulk and single-cell antibody repertoires paired with single-cell transcriptomics of human B cells undergoing affinity maturation. We define unique gene expression and antibody repertoires of known and novel B cell states, including a pre-germinal centre state primed to undergo class switch recombination. We dissect antibody class-dependent gene expression of germinal centre and memory B cells to find that class switching prior to germinal centre entry dictates the capacity of B cells to undergo antibody-based selection and differentiate. Together, our analyses provide unprecedented resolution into the gene expression and selection dynamics that shape B cell-mediated immunity.
Keywords: antibody, repertoire, B cell, germinal centre, affinity maturation, single-cell genomics, human immunology
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