Thereza Imanishi-Kari, PhD

Tufts University School of Medicine, Boston, MA

2006 B Cells

Thereza Imanishi-Kari, PhDUntil recently, most research on the auto-reactive B cells that produce tissue-destroying antibodies in lupus has focused on "mature" B cells—meaning the cells already have learned which substance (antigen) they will react to.

With LRI funding, Dr. Imanishi-Kari pursued the novel idea that some immature B cells are in fact the source of destructive antibodies in lupus. She also looked at the participation of the protein, interferon, in forming these immature B cells.

Discovery: Early Immune System Error Challenges Basic B-Cell Biology in Lupus

In the journal Immunity in 2007, Dr. Imanishi-Kari reported a startling finding: that early mutation of immature, undeveloped B cells may indeed prevent them from becoming a source of tissue-destroying antibodies.

The discovery challenges that long-held dogma and changes basic views of B-cell biology in lupus since scientists had long thought that only “mature” B cells could mutate their antibody genes.

Dr. Imanishi-Kari also discovered that B cells mutate during their early development.  This early genetic altering of antibodies could prevent the developing cells from making an early immune system error—a mistake in “tolerance”—that causes autoimmune diseases such as lupus.

Dr. Imanishi-Kari’s discovery offers a new direction for research into autoimmunity.  It may explain why the immune system in lupus makes a basic mistake:  it fails to recognize its real enemies, and turns on itself—a core error in the autoimmune process.

The study results may also pave the way to new strategies for preventing lupus.

“Research on the basic biology of B cells has been somewhat neglected and underfunded. The LRI’s funding of novel research in this area has played a key role in high-profile discoveries. B cells are absolutely pivotal to lupus, and any important new insights into how they develop and function are very helpful in creating the ‘blueprints’ by which we can understand dysfunction in lupus. This study advances our understanding of both normal and pathogenic B-cell responses. Its results could point to how to interfere with them in lupus.”

– Mark Shlomchik, MD, PhD, Professor of Laboratory Medicine and Immunobiology, Yale University School of Medicine

Select publications:

Class switch recombination and somatic hypermutation in early mouse B cells are mediated by B cell and Toll-like receptors. Han JH, Akira S, Calame K, Beutler B, Selsing E, Imanishi-Kari T. Immunity. 2007 Jul;27(1):64-75. Epub 2007 Jul 19.

Ongoing funding:

As a result of her LRI-funded work, Dr. Imanishi-Kari was awarded a $300,000 grant from NIH's NIAID to continue this research.