Studies of congenitally immunologic mutant New Zealand mice. I. Autoimmune features of hereditarily asplenic (Dh/+) NZB mice; reduction of naturally occurring thymocytotoxic antibody and normal suppressor function

M. E. Gershwin, J. J. Castles, R. M. Ikeda, K. Erickson, J. Montero

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17 Scopus citations

Abstract

Hereditarily asplenic (Dh/+) New Zealand Black (NZB) mice were produced by initial mating with B6CBA Dh/+ mice, followed by backcrossing, including H-2 typing and parental selection, with a colony of NZB mice. NZB Dh/+ mice, in their F 6, F 7, and F 8 generation, were serially followed and compared to +/+ littermates. With age, NZB Dh/+ and +/+ mice develop a similar frequency of anti-erythrocyte and anti-nuclear, SS DNA, native DNA and poly I.poly C antibodies. Furthermore, renal histology is unchanged in NZB Dh/+ compared to +/+ mice. However, in striking contrast, NZB Dh/+ mice have a significantly reduced degree of hypergammaglobulinemia, a delayed onset and lower titer of naturally occurring thymocytotoxic antibody (NTA), and a reduction in both diffuse lymphocytic infiltrates and lymphoma. Moreover, although NZB Dh/+ mice lose a significant degree of T helper function with age, as manifest by reduced responsiveness to T cell mitogens, SRBC, and skin allogrfts, they appear to retain antigen nonspecific suppressor function. Thus, NZB Dh/+ mice develop autoimmune disease without influence by NTA and without premature loss of suppressor cell function. These results suggest that several of the authors' present concepts regarding NTA, autoimmunity, and lymphoma in NZB mice need re-examination. Indeed, it appears that several features of NZB immunopathology, including development of NTA and lymphoma, are not directly related to the primary appearance of autoimmune disease.

Original languageEnglish (US)
Pages (from-to)710-717
Number of pages8
JournalJournal of Immunology
Volume122
Issue number2
StatePublished - 1979

ASJC Scopus subject areas

  • Immunology

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