Human Milk-Derived B Cells: A Highly Activated Switched Memory Cell Population Primed to Secrete Antibodies

Abstract

While secretory Abs have been extensively explored in human breast milk, the existence, features, and functions of B lymphocytes remain largely unexplored in this compartment. We analyzed breast milk and blood lymphocytes from 21 lactating women, including 12 HIV-1-infected mothers. Breast milk B cells displayed a phenotype of class-switched memory B cells, with few IgD(+) memory and naive B cells. We observed that breast milk B lymphocytes bore a unique profile of adhesion molecules (CD44(+), CD62L(-), alpha(4)beta(7)(+/-), alpha(4)beta(1)(+)). Higher percentages of activated B cells (CD38(+)), large-sized B cells, plasmablasts, and plasma cells (CD19(+), CD20(low/-), CD27(high), CD138(+)) were found as compared with blood. This indicates that a significant proportion of breast milk B cells underwent terminal plasma cell differentiation. We also observed a higher frequency of cells secreting Ig spontaneously in breast milk. Among these cells, IgG-secreting cells predominated over IgA-secreting cells as measured by Ig ELISPOT assays. Specific Ab-secreting cells were investigated following polyclonal activation using the CD40L ligation. Finally, the detection of anti-HIV-1-secreting cells demonstrates the existence of B cells specific to HIV-1 Ag in breast milk from HIV-1-infected women. Breast milk B cells display a phenotype strikingly different from blood, are primed to secrete Abs, and have a mucosal homing profile similar to B cells located in gut-associated lymphoid tissue.

HIV-Specific Functional Antibody Responses in Breast Milk Mirror Those in Plasma and Are Primarily Mediated by IgG Antibodies

“…Plasma cells secreting HIV-specific IgG antibodies can be detected in breast milk (63), and differences in the specific activity of IgG between milk and plasma have been described, suggesting a compartmentalization of the IgG response in breast milk (4). This difference was marked by lower antigp160 and higher anti-gp120 responses in breast milk than in plasma.…”

High Cell-Free Virus Load and Robust Autologous Humoral Immune Responses in Breast Milk of Simian Immunodeficiency Virus-Infected African Green Monkeys

“…Furthermore, the comparable neutralization potencies of purified milk and plasma IgG of AGMs are in contrast to the poor neutralization potency of milk IgG compared to that of plasma IgG of RMs during chronic SIV infection (40). Although plasma IgG transudate predominantly contributes to the pool of milk IgG in primates (7,8), IgG-producing B cells are found in milk and contribute to a portion of the IgG found in milk (7,56). Therefore, the locally produced IgG in milk of AGMs may be more effective at autologous virus neutralization than that of RMs.…”

Maternal immunisation: collaborating with mother nature

“…Breast milk IgG originate from serum through FcRn transport and from milk resident B 1 lymphocytes (105). Total breast milk IgG concentration is about 10% of IgA concentration 2 but it tends to increase with duration of breastfeeding (100, 106,107).…”

“…Breast milk B lymphocytes are IgG producing memory 19 cells. Their antigen-specificity was demonstrated in the context of HIV infection (105). 20 Similarly, HIV-specific CD4 and CD8 T lymphocytes were detected in breast milk and may 21 contribute to virus control through inflammatory cytokines and cytotoxicity (117,118).…”