Advanced Course in Immunology On Demand Lecture Recordings-B Cell Tolerance and Autoimmunity

Video Transcription

Video Summary

The lecture examined how B cells contribute to autoimmunity and how the immune system normally restrains self-reactive B cells. It began with clinical evidence that B-cell depletion therapies, such as rituximab, can improve rheumatoid arthritis and multiple sclerosis, showing that B cells are important not only for antibody production but also for antigen presentation and cytokine production.<br /><br />A major focus was B-cell tolerance. In the bone marrow, self-reactive B cells are controlled mainly by receptor editing, which replaces their light chain to reduce self-reactivity; deletion is a backup mechanism. In the periphery, self-reactive B cells can become anergic, remaining alive but functionally silenced. Anergy involves dampened BCR signaling, reduced PI3K/PIP3 activity, low calcium signaling, and selective NFAT-driven transcription without full activation. IgM and IgD help regulate this process, with IgM more sensitive to monovalent self-antigen and IgD less so.<br /><br />The talk then explained how tolerance is broken in disease. Autoimmunity can arise when self-reactive B cells receive an inappropriate “second signal,” often through toll-like receptors that recognize nucleic acids in immune complexes. This is especially relevant in lupus, where anti-nuclear antibodies are central. TLR7 gain-of-function and X-linked gene dosage may help explain the strong female bias in lupus.<br /><br />Finally, the lecture highlighted that some lupus autoantibodies appear to come from short-lived, extrafollicular B-cell responses rather than germinal centers. This makes B-cell depletion or even CAR T-cell approaches potentially powerful, because they can reduce pathogenic B cells and may partially “reset” the immune system.

Asset Subtitle

Lecture 13: Julie Zikherman, University of California, San Francisco, School of Medicine

B Cell Tolerance and Autoimmunity

Asset Caption

Julie Zikherman, University of California, San Francisco, School of Medicine
B Cell Tolerance & Autoimmunity

Keywords

B cells

autoimmunity

B-cell depletion

rituximab

rheumatoid arthritis

multiple sclerosis

B-cell tolerance

receptor editing

anergy

toll-like receptors

lupus

anti-nuclear antibodies

CAR T-cell therapy