B-cell biology and development

Many different lines of genetically engineered mice carrying germline mutations in immunologically important genes were and still are indispensable to study the molecular mechanisms regulating B-cell development, selection, and response. However, the comparison of mouse mutants with corresponding genetic defects in human subjects revealed significant differences between human and murine B cells with respect to early phases of development, subset composition, and responses to antigens. Human B-cell development, for instance, does not depend on IL-7, whereas mutations in genes like BTK and BLNK block maturation of human but not murine pre-B cells. Human subjects, but not mice, have circulating MZ B cells carrying somatic mutations right after birth, and human subjects have a large compartment of circulating class-switched memory B cells that is much smaller in adult mice. Because primates and rodents diverged from a common ancestor at least 65 million years ago, such differences reflect the adaptation of the respective immune systems to the different physiologies, the different life spans, the environment, pathogens, commensal agents, and so on.