Differential immune reactivity to stress in BALB/cByJ and C57BL/6J mice: In vivo dependence on macrophages

Inbred BALB/cByJ and C57BL/6J mice not only differ in their neuroendocrine and behavioral reactivity to stress, but also their ability to mount appropriate immune responses to various pathogens. Because evidence suggests that stress may bias humoral or cell-mediated immune responses in these mouse strains, we assessed the effects of acute (1 h) physical restraint on the humoral immune response to keyhole limpet hemocyanin (KLH). Restraint exposure in close proximity to immunization with KLH enhanced the number of primary antigen-specific IgM and IgG producing splenic B cells in BALB/cByJ mice, but not in C57BL/6J mice. These effects might be determined at the level of macrophage antigen presenting cells, because BALB/cByJ mice immunized with KLH as a particulate antigen (i.e., encapsulated in liposomes) displayed the same stressor enhanced antibody response as they did to free, unencapsulated KLH. In addition, these mice showed enhanced production of the IgG, subtype of IgG, but not the IgG, subtype. Conversely, stressed C57BL/6J mice revealed an enhanced IgG,, response, although this was observed only under conditions of immunization with liposome-encapsulated KLH. In a final experiment involving only the BALB/cByJ strain, the depletion of macrophages in the spleen by administration of liposomes containing dichloromethylene biphosphonate (DMDP) 2 days before immunizing the mice with free KLH and restraint exposure, blocked the restraint-induced enhancement of humoral immune responses. These data suggest a possible intermediary role for macrophages in stressor-induced immunomodulation in vivo, which may be a potential point of divergence that explains the differential immune reactivity to KLH of BALB/cByJ and C57BL/6J mice exposed to an acute stressor. (C) 1998 Elsevier Science Inc.