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 neuroendoc rine and behavioral reactivity to stress, but also their ability to mo unt appropriate immune responses to various pathogens. Because evidenc e suggests that stress may bias humoral or cell-mediated immune respon ses in these mouse strains, we assessed the effects of acute (1 h) phy sical restraint on the humoral immune response to keyhole limpet hemoc yanin (KLH). Restraint exposure in close proximity to immunization wit h KLH enhanced the number of primary antigen-specific IgM and IgG prod ucing splenic B cells in BALB/cByJ mice, but not in C57BL/6J mice. The se effects might be determined at the level of macrophage antigen pres enting cells, because BALB/cByJ mice immunized with KLH as a particula te antigen (i.e., encapsulated in liposomes) displayed the same stress or enhanced antibody response as they did to free, unencapsulated KLH. In addition, these mice showed enhanced production of the IgG, subtyp e 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 d ichloromethylene biphosphonate (DMDP) 2 days before immunizing the mic e 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 immunomodulatio n in vivo, which may be a potential point of divergence that explains the differential immune reactivity to KLH of BALB/cByJ and C57BL/6J mi ce exposed to an acute stressor. (C) 1998 Elsevier Science Inc.