Genome complexity: B cell antibody switch controls (Introduction)

by David Turell , Monday, April 04, 2022, 20:15 (746 days ago) @ David Turell

Two proteins involved:

https://phys.org/news/2022-04-two-faced-protein-inhibits-cell-receptor.html

"In a study published in March in Science Signaling, researchers from Tokyo Medical and Dental University (TMDU) have revealed that CD22, a crucial molecule in B cell signaling, switches from an inhibitory role to an activating role when B cell receptor (BCR) signaling is compromised due to a genetic defect that causes an immune disorder.

"Contact between BCRs and foreign invaders prompts B cells to make antibodies, and CD22 inhibits BCR signaling to keep B cells from inappropriately releasing antibodies. Interestingly, previous research suggests that this inhibition is regulated by binding of CD22 to other factors expressed on the same cell. In contrast, a protein called CD45 is a main activator of BCR signaling, and defects in the gene encoding CD45 cause an immunodeficiency syndrome.

"'CD45 normally enhances BCR signaling," explains Chizuru Akatsu, lead author on the study. "When CD45 is missing in laboratory cell lines, BCR signaling is dramatically decreased; however, signaling is not affected as severely in mice when CD45 is missing, which suggests that there is some kind of compensatory mechanism at work."

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"As it turns out, the cells in which signaling was restored expressed unusually high levels of BCR, which accounted for their ability to continue functioning relatively normally. BCR signaling occurs at low levels even in the absence of stimulation by foreign antigens, and this low-level steady-state signaling is required for B cell development and survival. Because BCR is an endogenous ligand of CD22, continuous CD22 binding to its ligands facilitates inhibition of steady-state BCR signaling by CD22. If BCR signaling is compromised by a defect such as CD45 deficiency, steady-state signaling is markedly reduced by the signaling defect together with the signal inhibition by CD22; therefore, only B cells that express high levels of BCR survive. Through this mechanism, CD22 paradoxically restores BCR signaling in immune-deficient B cells."

Comment: for some reason scientists are always surprised at how complicated controls are in managing the immune system response with antibodies. The molecules and the cells do not think, but are managed by carefully designed feedback loops for accuracy in production when required. The controls are damaged in autoimmune diseases.