An Update on the Evolutionary History of Bregs.

The relationship between the evolutionary history and the differentiation of Bregs is still not clear. Bregs were demonstrated to possess a regulatory effect on B cells. Various subsets of Bregs have been identified including T2-MZP, MZ, B10, IL10-producing plasma cells, IL10 producing plasmablasts, immature IL10 producing B cells, TIM1, and Br1. It is known that B cells have evolved during fish emergence. However, the origin of Bregs is still not known. Three main models have been previously proposed to describe the origin of Bregs, the first known as single-single (SS) suggests that each type of Bregs subpopulation has emerged from a single pre-Breg type. The second model (single-multi) (SM) assumes that a single Bregs gave rise to multiple types of Bregs that in turn differentiated to other Breg subpopulations. In the third model (multi-multi) (MM), it is hypothesized that Bregs arise from the nearest B cell phenotype. The link between the differentiation of cells and the evolution of novel types of cells is known to follow one of three evolutionary patterns (i.e., homology, convergence, or concerted evolution). Another aspect that controls differentiation and evolution processes is the principle of optimization of energy, which suggests that an organism will always use the choice that requires less energy expenditure for survival. In this review, we investigate the evolution of Breg subsets. We studied the feasibility of Breg origination models based on evolution and energy constraints. In conclusion, our review indicates that Bregs are likely to have evolved under a combination of SM-MM models. This combination ensured successful survival in harsh conditions by following the least costly differentiation pathway, as well as adapting to changing environmental conditions.