FIVE Microbes and B Cell Development

Animals and many of their chronic microbial inhabitants form relationships of symbiotic mutualism, which occurs when coexisting life-forms derive mutual benefit from stable associations. While microorganisms receive a secure habitat and constant food source from vertebrate hosts, they are required for optimal immune system development and occupy niches otherwise abused by pathogens. Microbes have also been shown to provide vertebrate hosts with metabolic capabilities that enhance energy and nutrient uptake from the diet. The immune system plays a central role in the establishment and maintenance of host–microbe homeostasis, and B lineage cells play a key role in this regulation. Here, I reviewed the structure and function of the microbiota and the known mechanisms of how nonpathogenic microbes influence B cell biology and immunoglobulin repertoire development early in life. I also discuss what is known about how B lineage cells contribute to the process of shaping the composition of commensal/mutualistic microbe membership. Advances in Immunology, Volume 125 # 2015 Elsevier Inc. ISSN 0065-2776 All rights reserved. http://dx.doi. org/10.1016/bs.ai. 2014.09. 005 155 1. MICROBIOTA 1.1. Overview of microbiota and microbiome Evolutionary pressures over millennia have resulted in complex interrelationships between animals and the microorganisms that inhabit them. Mutualistic and commensal microorganisms are particularly abundant in the gut lumen, where an estimated 10 bacteria reside (Savage, 1977). In humans, these microbes represent over 1000 different prokaryotic species belonging to a limited set of a dozen taxa and are dominated by Grampositive anaerobes (Ley, Peterson, & Gordon, 2006). The term “microbiota” is defined as the collection of microorganisms in a distinct location, such as the human gut. The term “microbiome” generally refers to the collective genes contained within the microbiota, which in the case of the human gut includes some 3 million unique genes (Qin et al., 2010) mostly from bacteria. Of the relatively few known bacterial phyla in the human gut, the two most prominent are the Firmicutes and Bacteroidetes (Human Microbiome Project Consortium, 2012; Ley et al., 2006; Qin et al., 2010). In terms of their relationship to their animal habitats, the microbiota in general have been shown to be stable, resilient, and specific (Palmer, Bik, DiGiulio, Relman, & Brown, 2007; Zaretsky et al., 2012). The microbiota that inhabit animal hosts are frequently described as commensal (one partner benefits while the other is unaffected), yet, as more light has been shed on animal/microbe interdependence, the term mutualist (both partners derive benefit) has been suggested to provide a more accurate description for the bulk of the nonpathogenic cohabitating microorganisms (Ley et al., 2006; McFall-Ngai et al., 2013). Sequencing efforts have produced large data sets revealing a diverse array of bacterial communities across various human body sites, diets, and populations and delineate the range of functional and structural configurations in healthy populations (Human Microbiome Project Consortium, 2012; Qin et al., 2010; Turnbaugh et al., 2007; Yatsunenko et al., 2012). These studies show substantial variability in microbial community structure between individuals in terms of microbial taxa, but a remarkable similarity between individuals in terms of the metagenomic makeup of imputed metabolic functions (Lozupone, Stombaugh, Gordon, Jansson, & Knight, 2012). In this regard, the overall contribution of imputed metabolic capabilities, rather than taxonomy, appears to influence the composition of microbial membership among the gut microbiota. 156 Duane R. Wesemann