Immunity system complexity: more B cell functions (Introduction)

by David Turell , Monday, November 27, 2023, 21:02 (151 days ago) @ David Turell

Just published:

https://phys.org/news/2023-11-team-protein-crucial-cell-differentiation.html

"Establishing proper communication between genes and far-away control switches at the right time in the right cell is not a small feat. In fact, very few proteins have the right combination of features to organize the genome into the right structures.

"In a new study published in Cell, scientists at La Jolla Institute for Immunology (LJI) and Massachusetts General Hospital, Harvard Medical School, show how a protein called IKAROS helps "weave" the genome into the correct structure required for B cell differentiation and generation of a life-saving repertoire of antibodies.

'"Without IKAROS, you cannot make a functioning B cell," says LJI Associate Professor Ferhat Ay, Ph.D., who co-led the new study.

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"'IKAROS acts at the root of this development and enables differentiation of the hematopoietic stem cell into a diverse set of immune cells including B cells," says Georgopoulos. These earlier studies showed that IKAROS-loss-of function mutations caused lymphoid malignancies in animal models and were associated with poor prognosis in children and young adults with B cell precursor leukemias.

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"The researchers found that IKAROS solves a big problem in B cell development. B cells use receptors with two "arms" to detect pathogens. These arms have a "light chain" region and a "heavy chain" region. When a B cell recognizes a pathogen, it churns out antibodies with matching arms.

" B cells assemble heavy chain regions fairly early in development. The Ay and Georgopoulos Labs found that assembling the light chain regions can be tricky because the genes encoding light chain development sit pretty far apart on the DNA. "This whole region needs to be rearranged in a proper 3D conformation," says Ay. "Something needs to bring them together."

"Fortunately, IKAROS is on the scene to help with some genome gymnastics. The two labs found that IKAROS binds to specific parts of the genome and controls the formation of very useful loops using these sites as anchors. This looping brings far-away genes together with their control elements, leading to the activation and expression of the genes needed for proper B cell development and light chain rearrangement. Just as important, this folding of the genome keeps other control elements away from genes that should not be expressed in a B cell.

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"The scientists emphasize that research into how chromatin is organized in the 3D space can help us understand how healthy cells develop—and how an improperly folded genome causes disease such as immunodeficiencies and cancer. Going forward, the researchers are interested in learning more about IKAROS disruption and disease development."

Comment: this ties in well with the previous entry on immunity. There are some B cells that routinely alter DNA to build an operative library of antibodies. This is a specific ability designed for an important function.