TY - JOUR T1 - A generalized quantitative antibody homeostasis model: regulation of B‐cell development by BCR saturation and novel insights into bone marrow function JF - bioRxiv DO - 10.1101/065730 SP - 065730 AU - József Prechl Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/07/26/065730.abstract N2 - In a pair of articles we present a generalized model for the homeostatic function of clonal humoralimmune system. Our model assumes that the essence of antibody homeostasis is to maintain a balance between the saturation of B‐cell receptors (BCR) by antigen and the saturation of antigen by antibodies. In this paper we describe the cycles of B-cell expansion and differentiation driven by BCR engagement maintenance.The fate of a B cell is determined by the signals it receives via its antigen receptor at any point of its lifetime. Starting with the expression of the surrogate light chain B cells go through several cycles of activation, proliferation, survival, antibody production all governed by BCR engagement. B cells move around to find a niche with antigens providing survival signal via the BCR. When they receive stronger-than-survival signals (antigen abundance) they produce antibodies or expand, their progeny competing for BCR mediated survival by different mechanisms in each niche. These include heavy chain production by rearrangement, light chain production by rearrangement, heavy chain class switching and affinity maturation. Transient downregulation of BCR is observed when cells cycle or receive other survival signals. By using this framework, free antigen concentration and apparent affinity as dimensions, for each niche we identify the mechanism of B1 cell development and we argue that bone marrow is more than a source of developing B cells but is rather the first organ to respond to antigen. This antigen is self at the early stages of life but includes non-self in adulthood. ER -