Somatically diversified and proliferating transitional B cells: implications for peripheral B cell homeostasis.

Area of Science:

• Immunology
• Developmental Biology
• Comparative Hematopoiesis

Background:

• Peripheral B cell homeostasis is typically maintained by continuous bone marrow B lymphopoiesis.
• In rabbits, bone marrow B lymphopoiesis ceases early in life, raising questions about long-term B cell maintenance.

Purpose of the Study:

• To investigate the mechanisms maintaining the peripheral B cell compartment in adult rabbits.
• To identify and characterize transitional B cell subsets in rabbits.

Main Methods:

• Identification and classification of rabbit transitional B cell subsets (T1 and T2) using flow cytometry (CD24, CD21).
• In vivo neutralization of B cell-activating factor (BAFF) to assess its role in B cell development.
• Analysis of B cell proliferation and Ig gene somatic diversification.

Main Results:

• Rabbit transitional B cells were classified into T1 (CD24highCD21low) and T2 (CD24highCD21+) subsets.
• Neutralizing BAFF arrested peripheral B cell development at the T1 stage.
• Proliferating T1 B cells with somatically diversified Ig genes, termed T1d B cells, were found in GALT, blood, and spleen of adult rabbits, persisting after B lymphopoiesis arrest.

Conclusions:

• A novel subset of transitional B cells (T1d) exists in rabbits that maintains peripheral B cell homeostasis.
• T1d B cells develop in the gut-associated lymphoid tissue (GALT), self-renew, and differentiate into mature B cells independently of bone marrow B lymphopoiesis.
• This discovery challenges conventional models of B cell maintenance and highlights species-specific immune strategies.