Birds' B-Cell Development: New Pathway Unveiled

Birds possess a specialized organ called the bursa of Fabricius which mammals do not have. It has long been thought that B cells, part of the immune system, are developed exclusively in this organ. However, researchers from Tohoku University have discovered a previously unknown pathway for B-cell development in chickens, overturning the long-standing belief

Details were published in Proceedings of the National Academy of Science of the United States of America on July 15, 2026.

"For more than half a century, this unique organ was considered the sole site of B-cell development in birds," stress Ryota Hirakawa, an assistant professor, and Tomonori Nochi, a professor, at Tohoku University's Graduate School of Agricultural Studies. "We discovered that a distinct population of B cells originates in the bone marrow of chickens and migrates directly to the cecal tonsils, bypassing the bursa of Fabricius entirely."

Hirakawa and his colleagues revealed that after the B cells become established in the cecal tonsils - tissues in a bird's gut that protect the intestinal tract against viral and bacterial pathogens - the B cells transform into IgA-producing plasma cells that populate the intestinal mucosa. The antibody IgA is responsible for maintaining intestinal immune homeostasis by coating beneficial bacteria and preventing harmful microorganisms from crossing the intestinal barrier.

Discovery of an alternative pathway for B-cell development in chickens. ©Tomonori Nochi

To determine the biological significance of their landmark discovery, the team developed a modern where both the conventional bursa-dependent pathway and the newly discovered bursa-independent pathway were inhibited. Inhibition caused IgA production to cease, which in turn led to major alterations in the gut microbiota. Harmful bacteria proliferated, including Streptococcus alactolyticus, translocating from the intestine to the liver.

The bacterial invasion triggered liver inflammation and disrupted normal metabolic function, demonstrating that the two B-cell populations cooperate to establish an effective intestinal barrier and maintain gut-liver homeostasis.

Cooperation between two B-cell pathways establishes an intestinal IgA barrier that safeguards gut-liver homeostasis. ©Tomonori Nochi

Tomonori Nochi says that the study comes at a time when antimicrobial resistance has become one of the greatest challenges facing livestock and poultry production worldwide. "Alternative, non-antibiotic strategies are needed for avian disease prevention. But to develop them, we need a more complete understanding of the immune system of birds. The findings in our study not only challenge our fundamental understanding of avian immunology, but also elucidate how intestinal immunity develops and protects the host."

Looking ahead, the researchers seek to identify the molecular and environmental factors that stimulate both the conventional bursa-dependent and the newly discovered bursa-independent B-cell developmental pathways. Targeting these two complementary pathways could lead to ways to enhance intestinal IgA production and establish immune- and microbiota-based strategies that promote healthy poultry development.

The study was conducted in collaboration with Kyoritsu Seiyaku Corporation, which hosts the Joint Research Laboratory of Animal Mucosal Immunology at Tohoku University, and GENODAS Inc.

Publication Details:

Title: Bursa of Fabricius-independent B cells establish an IgA-mediated intestinal barrier that safeguards gut-liver homeostasis

Authors: Ryota Hirakawa, Motoshi Hisamatsu, Sayoko Maekawa, Eiki Asai, Miyuko Ohta, Ayumi Matsuo, Kunihiro Okano, Toh Miyazaki, Motofusa Akiyama, Masaaki Toyomizu, Jahidul Islam, Mutsumi Furukawa, Tomonori Nochi

Journal: Proceedings of the National Academy of Sciences of the United States of America (PNAS)

DOI: 10.1073/pnas.2605569123

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