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Updated: Aug 10, 2026
Induction and Assessment of Class Switch Recombination in Purified Murine B Cells
Published on: August 14, 2010
B lymphocyte stimulator activates p38 mitogen-activated protein kinase in human Ig class switch recombination
Takechiyo Yamada1, Ke Zhang, Akiko Yamada
1Division of Clinical Immunology, Department of Medicine, UCLA School of Medicine, 10833 Le Conte Ave, Los Angeles, CA 90095-1680, USA. ymdtkcy@fmsrsa.fukui-med.ac.jp
Insights
B lymphocyte stimulator (BLyS) activates p38 MAPK, crucial for inducing immunoglobulin class switch recombination (CSR) and activation-induced cytidine deaminase (AID) expression in human B cells.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- B lymphocyte stimulator (BLyS) is a tumor necrosis factor ligand superfamily member with significant costimulatory effects on B cells.
- Understanding BLyS signaling is key to elucidating mechanisms of B cell activation and antibody diversification.
Purpose of the Study:
- To investigate the role of BLyS in immunoglobulin (Ig) class switching in human B cells.
- To determine if BLyS signaling influences stress-activated protein kinases and induces Ig class switch recombination (CSR) and activation-induced cytidine deaminase (AID) expression.
Main Methods:
- Human B cells were treated with BLyS to assess phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK).
- Ig class switching was evaluated by measuring switch circle transcripts (CTs) and AID expression, with and without IL-4 or IL-10.
- The effect of p38 MAPK inhibition using SB203580 on BLyS-induced CSR and AID expression was assessed via switch vector assays.
Main Results:
- BLyS induced p38 MAPK and JNK phosphorylation in human B cells.
- BLyS, in combination with IL-4, promoted switch circle transcripts (CTs) for IgG subclasses and IgE, and strongly induced AID expression.
- Inhibition of p38 MAPK signaling with SB203580 significantly reversed BLyS-induced CSR and AID expression, confirming the pathway's essential role.
Conclusions:
- BLyS-activated p38 MAPK is a critical mediator of AID expression and immunoglobulin class switch recombination (CSR) in human B cells.
- These findings highlight a specific molecular mechanism by which BLyS influences B cell function and antibody production.
Abstract:
B lymphocyte stimulator (BLyS), a member of the tumor necrosis factor ligand superfamily, has potent costimulatory activity on B cells. To investigate BLyS signaling in Ig class switching, we examined whether BLyS could control stress-activated protein kinases in human B cells as well as whether BLyS could induce human Ig class switch recombination (CSR) and expression of activation-induced cytidine deaminase (AID). BLyS induced the phosphorylation p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) in human B cells. As evidence of Ig class switch, BLyS plus interleukin (IL)-4 induced generation of switch circle transcripts (CTs) to gamma 1-2, gamma 4, and epsilon, whereas BLyS plus IL-10 induced gamma 1-2 CTs only. BLyS strongly induced AID expression in the presence of IL-4. Treatment with SB203580, a specific inhibitor of p38 MAPK signaling, almost completely reversed BLyS-induced CSR and AID expression in human B cells. The switch vector assay also showed that BLyS induced CSR in the presence of IL-4 in Ramos 2G6 human B cells and that SB203580 reversed CSR. These results indicate that BLyS-activated p38 MAPK plays an essential role in BLyS-induced AID-expression and CSR in human B cells.
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