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Updated: Jul 16, 2026
Isolation and Activation of Murine Lymphocytes
Published on: October 30, 2016
Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion
Menno C van Zelm1, Tomasz Szczepanski, Mirjam van der Burg
1Erasmus MC, Department of Immunology, 3015 GE Rotterdam, Netherlands.
Insights
This study quantifies B lymphocyte proliferation using kappa-deleting recombination excision circles (KREC). Naive B cells proliferate homeostatically, while T cell-dependent responses show higher proliferation and mutation, crucial for humoral immunity.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- The role of B lymphocyte proliferation in maintaining immune balance and responding to antigens is not fully understood.
- Quantifying B cell replication history is essential for understanding immune system dynamics.
Purpose of the Study:
- To quantify the replication history of mouse and human B lymphocyte subsets.
- To elucidate the contribution of proliferation to B lymphocyte homeostasis and antigen responses.
- To investigate the differences between T cell-dependent and T cell-independent B cell proliferation.
Main Methods:
- Utilized kappa-deleting recombination excision circles (KREC) to calculate the ratio of coding joints to signal joints, quantifying replication history.
- Validated the KREC method with in vitro proliferation studies.
- Analyzed B lymphocyte subsets from both mice and humans.
Main Results:
- Naive mature B lymphocytes, unlike transitional B cells, proliferate in vivo without somatic mutations.
- T cell-dependent B cell proliferation is significantly higher and exhibits more somatic hypermutation than T cell-independent responses.
- Antigen-experienced B cells in adults show greater proliferation and somatic hypermutation than in children, suggesting cumulative antigen exposure.
Conclusions:
- Proliferation significantly contributes to both B lymphocyte homeostasis and antigen-induced expansion.
- These findings highlight the importance of proliferation in humoral immunity.
- Understanding B cell proliferation aids in predicting peripheral B cell regeneration and identifying immunodeficiency defects.
Abstract:
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.
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