B Cell Strategies of Ag Recognition in a Stratified Immune System

From the old good times in which pioneering immunologists were simply specialised in either T or B lymphocytes, to the current lymphoid complexities that powerful quantitative technologies have revealed, the adaptive immune system has become a highly complicated subject of study. Also, as a part of the hematopoietic system, the lymphoid tissue is constituted by cells that undergo great turnover rates, with continuous renewal during an individual’s lifespan, extending from immature, bone marrow-derived precursors up to the final exhaustion of highly-differentiated cells. To exert their functions, B and T lymphocytes first need to recognise small molecular epitopes, through their highly diverse clonotypic receptors, with different degrees of specificity (the result of combinatorial gene rearrangements, with inexact joining ends). But lymphocytes also bear an evolutionary history that “informs” them about those more or less efficient receptor choices that previously influenced the survival of the species. Those cellular adjustments that were previously successful have remained preserved and are therefore preferentially exploited by the immune system (IS). Subsequently, immune strategies to “see” the antigenic world (self or foreign, harmless or dangerous) are balanced between an unrestricted openness to novelty (which has been named the promethean character of the IS [1]) and the evolutionary preservation of cellular activities and receptors that have already been tested and demonstrated their utility. In the following pages, we try to provide a few insights regarding when and where those functional polarisations are at work, with a special focus on B lymphocytes. We will leave out the differentiation steps and genetic programmes leading to the production of mature B lymphocytes, except in those selected cases when they may provide relevant information.