Speculations on the evolution of humoral adaptive immunity

Abstract

The protection of a multicellular organism from infection, at both cell and humoral levels, has been a tremendous driver of gene selection and cellular response strategies. Here we focus on a critical event in the development of humoral immunity: The transition from principally innate responses to a system of adaptive cell selection, with all the attendant mechanical problems that must be solved in order for it to work effectively. Here we review recent advances, but our major goal is to highlight that the development of adaptive immunity resulted from the adoption, reuse and repurposing of an ancient, autonomous cellular program that combines and exploits three titratable cellular fate timers. We illustrate how this common cell machinery recurs and appears throughout biology, and has been essential for the evolution of complex organisms, at many levels of scale.

Molecular control of the lymphocyte death timer

“…We anticipate that multiple signals can be processed to add to the time for division, by expression of Myc, and the time for death, by expression of protein ensemble components, to alter the overall immune response dynamics. Combination signaling through BCR, TCR, cytokines and other costimuli will enhance the initial production rate of the critical proteins and alter the final dynamics in B and T cells, in a manner we expect to have been optimized during evolution to generate and match an appropriate rate of expansion and timed loss of cells to the level of threat 58 . By this logic it is unsurprising that the molecular regulators found to control the cell death timer and division destiny timer are well known, evolutionarily conserved proteins, whose regulation is tightly controlled and frequently dysregulated in lymphoma.…”

Kevin Lafferty and the lymphocyte costimulator: theory and practice in Canberra

“…I have continued to try to build on ideas from those early days to develop, with colleagues, a clonal selection theory that will include “class” regulation. While not yet finished, the prospect of reconciling Burnet and Lafferty's views, and formulating a unified clonal selection theory with “class” regulation, does seem within sight 42,43 …”

“…While not yet finished, the prospect of reconciling Burnet and Lafferty's views, and formulating a unified clonal selection theory with "class" regulation, does seem within sight. 42,43 Today, members of the Australian and New Zealand Society for Immunology Inc. (ASI) know the name Lafferty for the popular semiserious debate held at their annual scientific meeting. This is not by chance.…”

Genomic Stress Responses Drive Lymphocyte Evolvability: An Ancient and Ubiquitous Mechanism

“…[ 30,122 ] In addition to the co‐option of stress induced mutagenic systems as well as AID and RAG enzymes, the emergence of a clonally evolving immune cell population also required co‐option and reuse of ancient cellular fate timers and other control systems to mediate coordination of replicative and fate‐related decision‐making following cell activation. [ 123 ] All in all, a general picture emerges in which co‐option and reuse of ancient DNA processing genes, repair pathways and regulatory pathways allowed for the development of somatically evolvable adaptive immune cell populations.…”