Mast cells (MCs) are the key effector cells in immunoglobulin E (IgE) -mediated allergic disease such as atopic asthma, allergic rhinitis and atopic dermatitis, but also participate in a variety of IgE-independent biologic responses. MCs can produce and secrete mediators influencing various aspects of the biology of dendritic cells, T cells, and B cells thus acting like regulatory cells (Merluzzi et al., 2010). With the advent of the MC deficient mice and selective engraftment with in-vitro-generated bone marrow derived mast cells (BMMC), it was shown that these cells are critical for the initiation of acute inflammatory responses. In several models for acute inflammation, the recruitment of neutrophils turned out to be initiated by MCs, which are localized at site of infection (Doener et al., 2013). In this study we showed that neutrophils and MCs interact through cell-cell contacts and via soluble factors. This cross-talk is bidirectional resulting in neutrophils activation and down-regulation of some of MC functions. Since the two cells are known to be involved in regulation of B cells activation, proliferation and immunoglobulin secretion we further investigated the role of their crosstalk in regulation of B cell response. We demonstrated an increased B cells survival in presence of conditioned media of neutrophils-MC co-cultures probably due to an increased presence of soluble BAFF. To extend the study to effect of this cross-talk on adaptive immune response we performed an in vivo T-independent immunization in Wild Type mice, in mast cell-deficient KitW-sh/KitW-sh mice and KitW-sh/KitW-sh mice engrafted with bone marrow derived MC. In parallel T-independent immunization was performed in WT, KitW-sh/KitW-sh mice and in reconstituted KitW-sh/KitW-sh mice depleted for neutrophils and immunoglobulin production among mice groups was compared. We discovered that the MCs and neutrophils together seem to regulate Ig production after T-independent immunization in a reciprocal way.