Differential Recruitment of T- and IgA B-lymphocytes in the Developing Mammary Gland in Relation to Homing Receptors and Vascular Addressins

Abstract

The mammary gland (MG) develops new vasculature and is colonized by lymphocytes, primarily T-cells, during pregnancy. In contrast, during lactation it is colonized primarily by IgA-containing B-cells (c-IgA cells). To explain this difference, we analyzed the spatiotemporal relationships between lymphocytes that expressed peripheral or mucosal homing receptors (HR) and the location of their vascular counterreceptors using quantitative immunohistochemical techniques. We observed that the density of β7+/CD3+ T-cells varied with the amount of the mucosal addressin cell adhesion molecule-1 (MAdCAM-1)-stained area. Both increased during pregnancy to peak at delivery, decreased rapidly in early lactation to a steady level in mid- and late lactation, and returned to resting values after weaning. Although 60% of these β7+/CD3+ T-cells scattered in the epithelium co-expressed αEβ7, whereas the remaining 40% in association with blood vessels were α4β7, these results are consistent with a role of MAdCAM-1 in the localization of α4β7+ T-cells. In contrast to T-cells, β7+/c-IgA+ B plasmablasts (∼ 30% of total c-IgA cells) were located at the alveolar confluence, and their numbers increased in mid- and late lactation when MAdCAM-1 density plateaued. However, both T-and B-cells decreased after weaning. These results show an association between MAdCAM-1 expression level and recruitment of T-cells that does not hold for c-IgA B cells. Furthermore, the recruitment and accumulation of α4β7+ c-IgA cells are reminiscent of locally produced chemoattractants.