Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion
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- Menno C. van Zelm
- 1Erasmus MC, Department of Immunology
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- Tomasz Szczepański
- 1Erasmus MC, Department of Immunology
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- Mirjam van der Burg
- 1Erasmus MC, Department of Immunology
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- Jacques J.M. van Dongen
- 1Erasmus MC, Department of Immunology
Description
<jats:p>The contribution of proliferation to B lymphocyte homeostasis and antigen responses is largely unknown. We quantified the replication history of mouse and human B lymphocyte subsets by calculating the ratio between genomic coding joints and signal joints on kappa-deleting recombination excision circles (KREC) of the IGK-deleting rearrangement. This approach was validated with in vitro proliferation studies. We demonstrate that naive mature B lymphocytes, but not transitional B lymphocytes, undergo in vivo homeostatic proliferation in the absence of somatic mutations in the periphery. T cell–dependent B cell proliferation was substantially higher and showed higher frequencies of somatic hypermutation than T cell–independent responses, fitting with the robustness and high affinity of T cell–dependent antibody responses. More extensive proliferation and somatic hypermutation in antigen-experienced B lymphocytes from human adults compared to children indicated consecutive responses upon additional antigen exposures. Our combined observations unravel the contribution of proliferation to both B lymphocyte homeostasis and antigen-induced B cell expansion. We propose an important role for both processes in humoral immunity. These new insights will support the understanding of peripheral B cell regeneration after hematopoietic stem cell transplantation or B cell–directed antibody therapy, and the identification of defects in homeostatic or antigen-induced B cell proliferation in patients with common variable immunodeficiency or another antibody deficiency.</jats:p>
Journal
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- The Journal of Experimental Medicine
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The Journal of Experimental Medicine 204 (3), 645-655, 2007-02-20
Rockefeller University Press
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Details 詳細情報について
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- CRID
- 1360011143615241472
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- ISSN
- 15409538
- 00221007
- http://id.crossref.org/issn/00221007
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- Data Source
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- Crossref