Prolactin (PRL) is the primary lactogenic pituitary hormone that plays an e
ssential role in many aspects of reproduction, from fertilization to mammar
y gland development and maternal behavior. PRL has also been reported to pl
ay a role in immunoregulation, Because initial observations indicated that
hypophysectomized rats present abnormalities of the immune system, includin
g increased thymic atrophy and lymphopenia, a number of studies have focuse
d on the potential immunomodulatory roles of PRL, This hormone exerts its b
iological activities following binding to specific cell surface PRL recepto
rs (PRLRs), In this report, we have characterized the development and funct
ion of the immune system in PRLR-deficient mice. Compared with wild-type co
ntrol mice, PRLR-/- mice demonstrate no alterations in thymic or splenic ce
llularity or in the composition of the lymphocyte subsets present in primar
y (bone marrow and thymus) or secondary (spleen and lymph nodes) lymphoid o
rgans. Lymphocytes from PRLR-/- mice are functional in vitro, as they can p
roliferate normally to mitogens, cytokines, and allogeneic cells. PRLR-/- s
plenocytes display normal NK-mediated cytotoxicity to YAC-1 target cells. I
n vivo studies have revealed that PRLR-/- mice are able to 1) generate norm
al steady-state Ig levels, 2) mount a normal specific Ig response following
immunization with a T-dependent Ag, 3) eliminate injected allogeneic tumor
cells, and 3) effectively control Listeria monocytogenes infection. Taken
together, these results show that immune system development and function pr
oceed normally in the absence of PRL-mediated signaling and suggest that PR
LR pathways are not essential for immunomodulation in vivo.