Human milk-derived B cells: a highly activated switched memory cell population primed to secrete antibodies.
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.
Tuaillon
Edouard
E
Unité de Recherche EA 4205, Université Montpellier 1, and Laboratoire de Virologie, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
Valea
Diane
D
Becquart
Pierre
P
Al Tabaa
Yassine
Y
Meda
Nicolas
N
Bollore
Karine
K
Van de Perre
Philippe
P
Vendrell
Jean-Pierre
JP
D000906:Antibodies / Q000032:analysis; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000032:analysis; D005260:Female; D015483:HIV Antibodies / Q000032:analysis; D015658:HIV Infections; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008895:Milk, Human / Q000276:immunology* / Q000821:virology; D010950:Plasma Cells
D000906:Antibodies; D015815:Cell Adhesion Molecules; D015483:HIV Antibodies; D007132:Immunoglobulin Isotypes