Maternal obesity shapes the B lymphocyte and antibody repertoires of human colostrum

ABSTRACT The prevalence of obesity is rapidly increasing worldwide and its impact on future generations must be assessed. We recently showed that colostrum from mothers with obesity contained a significantly reduced B lymphocytes (CD19 + ) fraction. Here, in a subsequent transversal cohort study of 48 mothers, we exhaustively characterize the B lymphocytes subsets present in peripheral blood and colostrum from obese mothers and describe a pervasive alteration of the B lymphocytes compartment of human colostrum accompanied by a dysregulated antibody composition. We describe significant decreases in regulatory B cells and soluble IgA concentrations, combined with increases in soluble IgG and double negative 2 (CD19 + , CD27 - , IgD - , CD38 - , CD24 - , CD21 - , CD11c + ) B lymphocytes. These alterations correlated with maternal BMI and corporal fat %. We provide evidence for possibly autoimmune IgG present in obese colostrum, and for the proinflammatory consequences of obese colostrum in vitro . Beyond the impact of obesity, we evidence the selective presence of B lymphocyte subtypes in colostrum and in situ production of IgG antibodies, which expands our current understanding of the origin of colostrum IgG. As maternal milk antibodies play a crucial role in regulating neonatal gut immune development, this work uncovers maternal obesity as a potential risk factor for compromised breastmilk immune components, calling for more research on the long-term health of lactating infants.