Autoimmune reactions and malignant changes in germ-free New Zealand Black mice.

Although NZB mice were bred and maintained in a germ-free environment their spleens enlarged and showed a sequence of histological events concomitant with the advent of positive antiglobulin (Coombs) reactions at 8–10 months which were similar to, but less intense than, those of their conventional NZB counterparts. The numerous large follicles with prominent germinal centres which developed in the white pulp and the proliferations of large pyroninophilic cells in the red pulp thus represented a humoral autoimmune reaction uncomplicated by external microbial antigenic stimuli. This burst of immunological activity in the spleen was followed by a reticulum cell neoplasia (apparently originating within the follicles and from the perifollicular mantles) which was transferable by intraperitoneal injection of spleen cell suspensions to syngeneic and allogeneic (BALB/c) recipients. By comparison, the inguinal lymph nodes of these same germ-free NZB mice were both immunologically inactive and exempt from the malignant process. Lesions in the thymus, and kidney lesions resembling human membranous glomerulonephritis or lupus nephritis, were found in both germ-free and conventional mice of this strain. Possible relationships between the autoimmunity, malignancy and the virus-like particles known to be present in germ-free NZB mice are discussed.