Clonal persistence of B lymphocytes in normal mice is determined by variable region-dependent selection

Area of Science:

• Immunology
• Cell Biology
• Genetics

Background:

• Adult splenic B cells typically undergo rapid apoptosis in adult recipient spleens.
• Newborn recipient environments promote B cell expansion and long-term survival.
• The peritoneal cavity environment in adult mice also supports B cell persistence.

Purpose of the Study:

• To investigate if B cell persistence in newborn hosts and adult peritoneal cavities involves selection based on expressed clonal specificities.
• To analyze the variation in VH gene family repertoires of donor B cells in different host environments over time.

Main Methods:

• Adoptive transfer of splenic B cells from lipopolysaccharide (LPS)-reactive mice into LPS-non-responder histocompatible recipients.
• Analysis of VH gene family repertoires using mRNA colony blot assays at various time points post-transfer.
• Comparison of B cell populations in newborn spleen and adult peritoneal cavity environments.

Main Results:

• Donor adult LPS-reactive B cells showed differential usage of VH genes in both newborn and adult peritoneal environments.
• B cells expressing J558 or VH11 gene families were positively selected for persistence and expansion.
• B cells expressing D-proximal, J606, and 36-30 VH gene families were less selected.

Conclusions:

• B cell persistence and expansion are primarily determined by selection through their immunoglobulin variable regions.
• This selection mechanism is independent of genetic properties associated with specific B cell subsets.
• The findings highlight the role of antigen-driven selection in shaping B cell populations in vivo.