Complexity of the human memory B-cell compartment is determined by the versatility of clonal diversification in germinal centers

Proceedings of the National Academy of Sciences of the United States of America
Bettina BudeusR Küppers

Abstract

Our knowledge about the clonal composition and intraclonal diversity of the human memory B-cell compartment and the relationship between memory B-cell subsets is still limited, although these are central issues for our understanding of adaptive immunity. We performed a deep sequencing analysis of rearranged immunoglobulin (Ig) heavy chain genes from biological replicates, covering more than 100,000 memory B lymphocytes from two healthy adults. We reveal a highly similar B-cell receptor repertoire among the four main human IgM(+) and IgG(+) memory B-cell subsets. Strikingly, in both donors, 45% of sequences could be assigned to expanded clones, demonstrating that the human memory B-cell compartment is characterized by many, often very large, B-cell clones. Twenty percent of the clones consisted of class switched and IgM(+)(IgD(+)) members, a feature that correlated significantly with clone size. Hence, we provide strong evidence that the vast majority of Ig mutated B cells--including IgM(+)IgD(+)CD27(+) B cells--are post-germinal center (GC) memory B cells. Clone members showed high intraclonal sequence diversity and high intraclonal versatility in Ig class and IgG subclass composition, with particular patterns of memory B-cell ...Continue Reading

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Jan 23, 2016·Current Opinion in Immunology·Lynn M Corcoran, David M Tarlinton
Apr 12, 2016·Current Opinion in Immunology·Scott D Boyd, James E Crowe
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Feb 5, 2021·The Journal of Experimental Medicine·Artur KiblerMarc Seifert
May 11, 2021·Clinical and Experimental Immunology·Yuzi LiFanlei Hu
Jun 13, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bettina BudeusMarc Seifert
Oct 16, 2021·Frontiers in Immunology·M Christian TjiamMartyn A French
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