TY - JOUR
T1 - Cellular events in tolerance. VII. Decrease in tolerant spleens of PFC precursors stimulated in vitro by specific antigen or mitogen
AU - Venkataraman, M.
AU - Scott, David W.
N1 - Funding Information:
i Supported by USPHS Grant AI-10716. * Recipient of Research Career Development Award AI-00093.
PY - 1979/10
Y1 - 1979/10
N2 - Spleen cells from adult mice rendered tolerant to the fluorescein (FL) hapten (as FL-sheep γ-globulin) were analyzed at limiting dilution for the numbers of precursors stimulatable either by specific antigen (FL-polymerized flagellin; FL-POL) or by a polyclonal B-cell activator (E. coli lipopolysaccharide; LPS). As expected, the number of PFC presursors activated by FL-POL was reduced more than fourfold in the spleens of FL-tolerant mice compared to normal controls. In contrast, LPS was able to trigger equivalent numbers of "FL-specific" PFC precursors in both normal and tolerant spleens. However, the clones stimulated by LPS were predominantly the "low-avidity" precursors in FL-tolerant spleens as shown by plaque inhibition studies. In addition, after FL-gelatin enrichment of normal or tolerant spleen cells, which contain equal numbers of antigen-binding cells, we found that purified cells from tolerant mice were in fact reduced in the numbers of clonable precursors upon LPS stimulation. Two other B-cell mitogens, POL and PPD, also failed to activate PFC precursors from FL-gelatin-purified tolerant spleen cells. Our results suggest that some high-avidity clones may be functionally deleted even in adult B-cell tolerance as previously noted for neonatal tolerance.
AB - Spleen cells from adult mice rendered tolerant to the fluorescein (FL) hapten (as FL-sheep γ-globulin) were analyzed at limiting dilution for the numbers of precursors stimulatable either by specific antigen (FL-polymerized flagellin; FL-POL) or by a polyclonal B-cell activator (E. coli lipopolysaccharide; LPS). As expected, the number of PFC presursors activated by FL-POL was reduced more than fourfold in the spleens of FL-tolerant mice compared to normal controls. In contrast, LPS was able to trigger equivalent numbers of "FL-specific" PFC precursors in both normal and tolerant spleens. However, the clones stimulated by LPS were predominantly the "low-avidity" precursors in FL-tolerant spleens as shown by plaque inhibition studies. In addition, after FL-gelatin enrichment of normal or tolerant spleen cells, which contain equal numbers of antigen-binding cells, we found that purified cells from tolerant mice were in fact reduced in the numbers of clonable precursors upon LPS stimulation. Two other B-cell mitogens, POL and PPD, also failed to activate PFC precursors from FL-gelatin-purified tolerant spleen cells. Our results suggest that some high-avidity clones may be functionally deleted even in adult B-cell tolerance as previously noted for neonatal tolerance.
UR - http://www.scopus.com/inward/record.url?scp=0018682853&partnerID=8YFLogxK
U2 - 10.1016/0008-8749(79)90342-3
DO - 10.1016/0008-8749(79)90342-3
M3 - Article
C2 - 314857
AN - SCOPUS:0018682853
SN - 0008-8749
VL - 47
SP - 323
EP - 331
JO - Cellular Immunology
JF - Cellular Immunology
IS - 2
ER -