Demonstration of a B-lymphocyte mitogen produced by the Lyme disease pathogen, Borrelia burgdorferi.
Lyme disease refers to the multisymptomatic illness in humans which results from infection with the tick-borne spirochete Borrelia burgdorferi. The white-footed mouse is the major reservoir for B. burgdorferi and, upon infection, certain inbred mice develop symptoms similar to those reported in human disease. Sonicated preparations of washed spirochetes were found to have potent mitogenic activity when cultured with lymphocytes from naive C57BL/6, C3H/HeJ, or BALB/c mice. The activity of the B. burgdorferi sonicate was approximately fourfold greater than that of a similarly prepared Escherichia coli sonicate. Polymyxin B efficiently inhibited the mitogenic activity of the E. coli sonicate but only slightly inhibited that of the B. burgdorferi sonicate, suggesting that a lipid A-containing lipopolysaccharide was not responsible for the B. burgdorferi activity. Kinetic analysis indicated peak proliferation at 2 to 3 days of culturing, suggesting polyclonal activation. B- and T-lymphocyte depletion experiments indicated that the major cell type responding to the B. burgdorferi mitogen was the B lymphocyte. This mitogen stimulated murine B cells not only to proliferate but also to differentiate into antibody-secreting cells, as demonstrated by the production of immunoglobulin by stimulated splenocytes. Furthermore, the sonicated preparation stimulated the B-cell tumor line CH12.LX to secrete immunoglobulin in the absence of accessory cells. B. burgdorferi also stimulated interleukin-6 production in splenocyte cultures. The observation that B. burgdorferi can stimulate activation of and immunoglobulin production by normal B lymphocytes may directly reflect on the development of arthritis associated with persistent infection by this organism.
Schoenfeld
R
R
Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132.
Araneo
B
B
Ma
Y
Y
Yang
L M
LM
Weis
J J
JJ
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D007136:Immunoglobulins / Q000096:biosynthesis; D008193:Lyme Disease / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008934:Mitogens / Q000032:analysis* / Q000502:physiology; D011112:Polymyxin B / Q000494:pharmacology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology
D007136:Immunoglobulins; D008934:Mitogens; D011112:Polymyxin B