Immunity system complexity: B cell controls (Introduction)

by David Turell , Thursday, September 23, 2021, 18:05 (1289 days ago) @ dhw

They make new antibodies when stumulated:

https://medicalxpress.com/news/2021-09-antibody-producing-cells-predestined-fates.html

"During an infection or after a vaccination, mature B cells form germinal centers, a sort of pop-up training facility. There, the cells mutate and rearrange their antibody-encoding genes, until they either produce an improved antibody or die trying. The process is central to the body's responses to many pathogens, but it's also fraught with danger; poorly-placed B cell mutations can cause lymphoid cancers.

"'All of our cells have defense mechanisms against becoming mutated, but B cells actually do the opposite; they specialize in mutating, and they do it very fast," said co-senior author Dr. Ari Melnick, the Gebroe Family Professor of Hematology / Oncology and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.

"Previous studies showed that B cells control their germinal center maturation by altering the accessibility of different parts of their genomes, and triggering cascades of gene expression changes to direct and limit their development. But what coordinates all of those signals?

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"By developing new computational methods, the team was able to deconvolute the changes to identify OCT2 as the molecule that appeared to be at the root of the process.

"But the distribution of OCT2 in germinal centers was surprisingly similar to its distribution in mature B-cells prior to their activation. Probing B cells with new genomic and molecular tools in the lab, the researchers found OCT2 in immature B cells pre-positioned in the genome locations where it would later operate during the germinal center reaction. Another gene regulatory protein, OCA-B, triggers the genome locations marked by OCT2 to become active, turning them into "super-enhancers" that drive the rest of the B cell maturation regulatory network.

"'The destiny of the cell is predetermined in a way, so that if it gets the right signal, it will know how to create the germinal center B cell," said Dr. Melnick.

"The notion of cellular predestination—and the identification of a specific mechanism for it—may be the paper's most far-reaching discovery.

"'I think that's potentially a profound finding that could apply to many different transitions between cell types," said co-senior author Dr. Olivier Elemento, who is director of the Caryl and Israel Englander Institute for Precision Medicine and associate director of the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine at Weill Cornell Medicine.

"During embryonic development, for example, a single cell divides and matures into all of the cells of a complete organism, following a series of branching decision points that may use similar mechanisms to mark super-enhancers for later activation."

Comment: These B cells are designed to act quickly, no actual thought involved. It is an irreducibly complex system designed all at once. It cannot be evolved by chance or step-by-step.