Spatial map of human B cell compartmentalization

Abstract We have performed a comprehensive analysis of human lymphoid tissue from relatively inaccessible sites including SPL, BM and LN from normal donors. Most of what is known about human B cells comes from blood, a tissue that contains only ~2% of the immune cells in the body. Examination of different tissues from 14 independent donors reveals for the first time the global B cell population structure. We performed unbiased computational clustering on samples stained with antibodies to markers indicative of antigen experience, activation status, and tissue retention. We found that the population structure of splenic B cells is remarkably conserved across a large number of donors who vary by age, gender, environment and history of pathogen exposure. By contrast, blood B cell composition is highly individualized with respect to each donor while BM has a relatively uniform population structure with some individual tailoring. Comparison of paired tissues within individuals further demonstrates that SPL and blood contain largely non-overlapping populations, suggesting geographic segregation of B cell subsets within each person. Recently published Ig clonal tracking studies from this donor cohort demonstrates partitioning of B cell clonal sharing into two broad networks, one across blood rich tissues and the other restricted to portions of the GI tract. Knowledge about the mechanisms that direct the trafficking and retention of discrete B cell subsets to specific tissues has direct implication to how infections are controlled throughout the body. Our findings constitute the basis for a geographic understanding of B cell population structure that will inform studies on the human humoral immune response.