Advanced Course in Immunology On Demand Lecture Recordings-B Cell Development

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Video Summary

The speaker delivers a late-evening lecture on B-cell biology, opening by honoring Mike Tankrow for his major contributions to the field, including B-cell development, survival, BAF/BAFF signaling, and the discovery of age-associated B cells.<br /><br />He begins with a short quiz about species differences in circulating B-cell abundance, then uses this to motivate a broad overview of B-cell development. The lecture traces B cells from hematopoietic stem cells in the fetal liver and bone marrow through early developmental checkpoints, transitional stages in the spleen, and finally to mature follicular or marginal zone B cells. He emphasizes that most B cells generated in the bone marrow die before reaching the periphery.<br /><br />A major theme is immunological tolerance and the historical development of the clonal selection theory, drawing on the work of Ray Owen, Frank Burnet, Peter Medawar, and Joshua Lederberg. He explains how experiments established that self-reactive lymphocytes are removed or silenced during development. Key experimental milestones include thymidine-labeling studies showing high production but major loss of B-cell precursors, hapten experiments demonstrating clonal abortion, and transgenic mouse studies showing deletion or anergy depending on the strength and form of self-antigen exposure.<br /><br />He also discusses transcription factors essential for B-cell lineage commitment, especially EBF and PAX5, showing how loss of PAX5 can cause B cells to de-differentiate into functional T cells.<br /><br />Finally, the lecture covers peripheral B-cell survival. The speaker explains that mature B cells depend on tonic B-cell receptor signaling and survival factors such as BAFF. Parabiosis experiments and mutant mouse models illustrate competition for survival niches in the periphery. He concludes by noting open questions about aging, plasma cell niches, and how B-cell depletion therapies affect long-term immunity.

Asset Subtitle

Lecture 7: Ali H. Ellebedy, Washington University School of Medicine

B Cell Development

Asset Caption

Ali H. Ellebedy, Washington University School of Medicine
B Cell Development

Keywords

B-cell biology

B-cell development

immunological tolerance

clonal selection theory

BAFF signaling

B-cell receptor signaling

PAX5

EBF transcription factor

transitional B cells

age-associated B cells

B-cell survival niches