ASSESSING A NOVEL HYPOTHESIS THAT B-CELL ERROR CATASTROPHE CAN CAUSE GERMINAL CE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Germinal centers are vital to a healthy immune response, yet surprisingly little is known about the factors that influence their persistence or loss. Here, we propose a novel hypothesis for their loss, namely, the propensity of B-cell populations under somatic hypermutation to succumb to error catastrophe. This hypothesis is made possible by recent theoretical developments that re-derive error catastrophe theory from an evolutionary perspective. In addition to testing this hypothesis against extensive simulation and experimental data, we also plan to extend our new theoretical developments to encompass evolutionary interactions between an infecting pathogen and the immune response that it evokes.