Immune Response Potential of Mast Cell-Deficient W/W^v Mice

Abstract

Immune responses of mast cell-deficient WBB6F₁-W/W^v mice and their mast cell-sufficient littermates (LM: WBB6F₁-W/+, W^V/+ and +/+) were compared. After a single intravenous injection of sheep erythrocytes (SE), polyvinylpyrrolidone or bacterial lipopolysaccharide, the antigen-specific IgM plaque-forming cell (PFC) response of W/W^v mice was similar to or greater than the response of LM mice. When both primary and secondary injections of SE or chicken γ-globulin were given to mice and antigen-specific IgG PFC responses quantified, the response of W/W^v again was similar to or greater than that of LM mice. Serum titers of antigen-specific IgE were higher in W/W^v than in LM mice after injections of ovalbumin in alum or infections of Nippostrongylus brasiliensis. Ovalbumin-sensitized W/W^v and LM mice developed active systemic anaphylaxis after ovalbumin challenge. The ability of W/W^v mice to be sensitized for and elicit contact sensitivity (CS) reactions was studied using picryl chloride or dinitrofluorobenzene as sensitizing and challenge agents and quantifying 24-hour reactions by change in ear thickness. SE or methylated bovine serum albumin was used to sensitize and challenge mice for delayed-type hypersensitivity (DTH) reactions which were quantified at 24 h by change in foot pad or ear thickness. CS and DTH reactions of W/W^v and LM mice were similar. No evidence of immune deficiency of W/W^v mice was found.

Role of mast cells in anaphylaxis. Evidence for the importance of mast cells in the cardiopulmonary alterations and death induced by anti-IgE in mice.

“…Third, anti-IgE represents a more specific mechanism than antigen challenge for initiating exclusively IgE-dependent processes, at least in actively immunized mice. Finally, two groups already had reported that fatal anaphylaxis could be elicited in mast cell-deficient mice challenged with specific antigen after active (22,23) or passive (24) sensitization, and we were searching for an approach to reveal potentially mast cell-dependent differences in the anaphylactic responsiveness of mast cell-deficient and normal mice.…”

“…A variety of cell types which can elaborate mediators similar or identical to those of mast cells (1-4, 19, 20), including basophils, monocytes/macrophages, eosinophils and platelets, also express receptors capable of binding IgE or aggregates of IgE (21). Moreover, "anaphylactic" syndromes leading to death from apparent cardiorespiratory collapse can be induced in genetically mast cell-deficient mice by appropriate sensitization procedures followed by challenge with specific antigen (22)(23)(24). On the other hand, anaphylactic reactions in both mast cell-deficient and normal mice have traditionally been assessed by clinical observations (prostration, death) rather than by actual measurements of pathophysiological responses (22)(23)(24).…”

“…Moreover, "anaphylactic" syndromes leading to death from apparent cardiorespiratory collapse can be induced in genetically mast cell-deficient mice by appropriate sensitization procedures followed by challenge with specific antigen (22)(23)(24). On the other hand, anaphylactic reactions in both mast cell-deficient and normal mice have traditionally been assessed by clinical observations (prostration, death) rather than by actual measurements of pathophysiological responses (22)(23)(24). As a result, the extent of the similarities between the pulmonary component of the responses elicited in mice and the anaphylactic reactions ofother experimental animals is unknown.…”

Recruitment of neutrophils during IgE-dependent cutaneous late phase reactions in the mouse is mast cell-dependent. Partial inhibition of the reaction with antiserum against tumor necrosis factor-alpha.

“…Moreover, Dolovich et al (36) reported that the early wheal responses induced by intracutaneous injection ofcodeine were rarely followed by clinically detectable late reactions, indicating that human cutaneous mast cell activation per se may not in all cases be sufficient for production ofa LPR. Finally, three groups have reported that fatal systemic anaphylaxis can be elicited in appropriately sensitized genetically mast cell-deficient mice that are virtually devoid of mast cells (37)(38)(39). Passive transfer studies indicate that the antibodies responsible for these reactions are of the IgE class (40).…”

Mast Cell-Independent Mechanisms of Immediate Hypersensitivity: A Role for Platelets

“…However, several studies suggest that mast cell degranulation is not the only mechanism involved in hypersensitivity reactions (6 -10). For example, several groups have reported that fatal systemic IgG-or IgE-mediated anaphylaxis can be elicited in mast celldeficient mice (7)(8)(9). It is possible that the small number of mast cells present in W/W v mice (Ͻ1% in skin; none elsewhere) is sufficient to induce fatal anaphylactic shock.…”