Journal
INTERNATIONAL IMMUNOLOGY
Volume 25, Issue 12, Pages 683-695Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxt030
Keywords
Antibody repertoire; memory B cells; secondary response; somatic hypermutation
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Funding
- National Institute of Allergy and Infectious Diseases (NIAID) [AI064752]
- Grants-in-Aid for Scientific Research [23380073] Funding Source: KAKEN
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High-affinity memory B cells are preferentially selected during secondary responses and rapidly differentiate into antibody-producing cells. However, it remains unknown whether only high-affinity, mutated memory B cells simply expand to dominate the secondary response or if in fact memory B cells with a diverse V-H repertoire, including those with no mutations, accumulate somatic mutations to create a new repertoire through the process of affinity maturation. In this report, we took a new approach to address this question by analyzing the V-H gene repertoire of IgG1(+) memory B cells before and after antigen re-exposure in a host unable to generate IgG(+) B cells. We show here that both mutated and unmutated IgG1(+) memory B cells respond to secondary challenge and expand while accumulating somatic mutations in their V-H genes in a stepwise manner. Both types of memory cells subsequently established a V-H gene repertoire dominated by two major clonotypes, which are distinct from the original repertoire before antigen re-exposure. In addition, heavily mutated memory B cells were excluded from the secondary repertoire. Thus, both mutated and unmutated IgG1(+) memory cells equally contribute to establish a new antibody repertoire through a dynamic process of mutation and selection, becoming optimally adapted to the recall challenge.
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