Neonatal life is characterized by heightened sensitivity to infectious agents. The sensitivity to infectious diseases is caused by an immaturity of the immunes system which could be due to either qualitative or quantitative differences of neonatal and adult immune cells. In respect to the B cell compartment, several differences have been observed between adults and neonates, including differences in T cell dependent and independent immune responses. To better understand the differences between human neonatal and adult B cells one key question is whether these differences are caused by a different composition of the B cell subpopulations or whether single B cell subsets are intrinsically immature resulting in defective function. B cells have different functions that contribute to regular immune responses. The probably best studied function is the generation of antigen-specific antibodies. In addition to antibody production, B cells can also secrete cytokines and serve as antigen presenting cells. It has been demonstrated in mice that different developmental B cell stages possess very distinct functional characteristics. Much more limited data exist in respect to human B cells. Analysis of human cord blood has demonstrated that it mainly consists out of transitional B cells. Some mature B cells can also be identified based on phenotypical characteristics. But it remains controversial if they are already functionally mature suggesting that there might be also age-dependent functional differences in corresponding B cell subpopulations between neonates and adults. This indicates that it is crucial to understand the functional differences of both adult and neonatal B cell subpopulations when analyzing the mechanisms contributing to the immaturity of the neonatal B cell compartment. Thus, in the current proposal, B cell subpopulations from both neonates and adults will be investigated in respect to early proximal signaling, activation, production of immunoglobulins and cytokines, and the role of BAFF signals.