Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion

Menno C. Van Zelm, Tomasz Szczepański, Mirjam Van Der Burg, Jacques J M Van Dongen

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180 Citations (Scopus)


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 antigeninduced 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. JEM

Original languageEnglish
Pages (from-to)645-655
Number of pages11
JournalJournal of Experimental Medicine
Issue number3
Publication statusPublished - 19 Mar 2007
Externally publishedYes

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