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Memory B cells without somatic hypermutation are generated from Bcl6-deficient B cells
Hirochika Toyama1, Seiji Okada, Masahiko Hatano
1Department of Developmental Genetics (H2), Graduate School of Medicine, Chiba University, Chiba, Japan.
Immunity
|October 2, 2002
Summary
Germinal centers are essential for antibody maturation but not for generating memory B cells. Bcl6-deficient B cells lacking germinal centers still formed memory B cells, indicating germinal center-independent B cell development.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- High-affinity B cells develop in germinal centers after T cell-dependent antigen exposure.
- These B cells differentiate into memory B cells or long-lived antibody-forming cells.
- The precise role of germinal centers in this differentiation process remains debated.
Purpose of the Study:
- To investigate the necessity of germinal centers and Bcl6 for B cell differentiation into memory cells and antibody-forming cells.
- To determine if somatic hypermutation and Ig class switching are required for memory B cell generation.
Main Methods:
- Analysis of B cell differentiation in Bcl6-deficient mice, which lack germinal centers.
- Assessment of memory B cell populations (IgM, IgG1) in the spleen.
- Evaluation of long-lived antibody-forming cells in the bone marrow.
- Analysis of V-heavy gene mutations in memory B cells.
Main Results:
- Bcl6-deficient B cells formed IgM and IgG1 memory B cells in the spleen.
- These cells showed no mutations in their V-heavy genes.
- Differentiation into long-lived IgG1 antibody-forming cells in the bone marrow was significantly impaired.
- Memory B cell generation occurred independently of germinal center formation and somatic hypermutation.
Conclusions:
- Bcl6 and germinal center formation are crucial for somatic hypermutation and antibody affinity maturation.
- Memory B cell generation can proceed independently of germinal center formation, somatic hypermutation, and Ig class switching.
- This suggests distinct pathways for memory B cell development and antibody-producing cell differentiation.