scholarly journals Evidence for the clonal abortion theory of B-lymphocyte tolerance.

1975 ◽  
Vol 141 (4) ◽  
pp. 904-917 ◽  
Author(s):  
G J Nossal ◽  
B L Pike

This paper deals with the behavior of adult mouse bone marrow cells placed in tissue culture with or without antigen, and subsequently assessed for immune competence after adoptive transfer into lethally X-irradiated, syngeneic hosts. Attention was focussed on B lymphocytes through using hapten human gamma globulin (HGG) preparations as putative tolerogens in tissue culture, the T-cell-independent antigens DNP-POL and NIP-POL as challenge injections in adoptive hosts, and numbers of hapten-specific PFC in host spleens for the quantitation of immune competence. It was found that the capacity of bone marrow cells to mount an adoptive immune response rose by a factor of about fivefold over 3 days in tissue culture. This rise was completely abolished by the presence in the culture of hapten-HGG conjugates with about one mole of hapten per carrier molecule. The prevention of the emergence of immune competence amongst maturing B cells was termed clonal abortion tolerogenesis. Dose-response studies showed the lowest effective antigen concentration to be between 2.5 times 10- minus 10 and 2.5 times 10- minus 9 M, and a standard concentration of 2.5 times 10- minus 8 M was chosen as producing near maximal effects. The tolerance was antigen-specific and time-dependent, being maximal only when antigen was present continuously as the cultured cells was maturing. It did not depend on the presence of T lymphocytes in marrow, and was not of an "infectious" type. In contrast to tolerogenesis of mature B lymphocytes by high antigen concentrations, it could not be abolished by lipopolysaccharide. We speculate that clonal abortion may be a tolerance mechanism of great physiological significance for self-recognition, and discuss the results in the framework of other recent tolerance models, including those involving receptor blockade and suppressor T cells.

1978 ◽  
Vol 148 (5) ◽  
pp. 1251-1270 ◽  
Author(s):  
W C Yang ◽  
S C Miller ◽  
D G Osmond

Radioautographic DNA labeling and rosetting techniques were combined to study the development of surface IgM, Fc, and complement receptors (FcR, CR) on small lymphocyte populations in mouse bone marrow. [3H]thymidine was either infused continuously to label newly formed cells for periods up to 4 days, or injected daily, 21--35 days before use, to label a sample of long-lived cells. Bone marrow cells were incubated with sensitized sheep erythrocytes to detect surface IgM, FcR, and CR, respectively, and examined radioautographically after cytocentrifugation. During [3H]thymidine infusion, marrow small lymphocytes lacking surface markers were the first to show [3H]thymidine labeling. Most of these cells became labeled by 4 days (IgM--ve, 89%; FcR--ve, 92%; Cr--ve, 88%). Labeling of small lymphocytes bearing surface IgM, FcR, and Cr began after an initial lag and increased to high values by 4 days (IgM + ve, 73%; FcR + ve, 82%; CR + ve, 83%). Labeled IgM + ve small lymphocytes formed progressively larger rosettes as cell age increased. Some proliferating large lymphoid cells formed rosettes for IgM, FcR, and CR. Labeled long-lived small lymphocytes expressed surface IgM, FcR, and CR, the incidence of each receptor being uniformly high (38--43%) and the rosettes tending to be larger than those formed by newly formed lymphocytes. In double-surface marker studies, FcR and CR rosettes were formed by some IgM--ve small lymphocytes as well as IgM + ve cells in the marrow. After transfusion of marrow cells from donor mice infused with [3H]thymidine for 24 h, many labeled newly formed lymphocytes homed into the splenic red pulp of unlabeled syngeneic recipients. Subsequently, these cells showed a rapid increase in the incidence of rosettes for surface IgM, FcR, and CR, together with a progressive enlargement of each type of rosette. Although all the labeled small lymphocytes recovered from the spleen developed both surface IgM and FcR by 3 days, only approximately one-half developed CR. The results demonstrate that most of the small lymphocytes bearing FcR, CR, and surface IgM in mouse bone marrow are newly formed indigenous cells. Each receptor becomes detectable by rosetting soon after the small lymphocytes are first produced. The newly formed, marrow-derived small lymphocytes are able to continue their development of surface IgM, FcR, and CR after migrating into the spleen, consistent with a maturation of primary B lymphocytes. In addition, the data indicate the genesis in mouse marrow of a non-B lineage of lymphocytes (notably, IgM--ve FcR + ve cells.). A minority of small lymphocytes bearing IgM, FcR, and CR in mouse marrow are long-lived cells, presumptive recirculating immigrants, differing in receptor status from the newly formed cells. The results are discussed with regard to the heterogeneity of marrow lymphocytes and proposed models of primary B lymphocyte and null lymphocyte production.


Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1836-1841 ◽  
Author(s):  
M Kobayashi ◽  
BH Van Leeuwen ◽  
S Elsbury ◽  
ME Martinson ◽  
IG Young ◽  
...  

Abstract Human bone marrow cells cultured for 21 days in the presence of recombinant human interleukin-3 (IL-3) produced up to 28 times more colony-forming cells (CFC) than could be obtained from cultures stimulated with granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage CSF (GM-CSF). IL-3-cultured cells retained a multipotent response to IL-3 in colony assays but were restricted to formation of granulocyte colonies in G-CSF and granulocyte or macrophage colonies in GM-CSF. Culture of bone marrow cells in IL-3 also led to accumulation of large numbers of eosinophils and basophils. These data contrast with the effects of G-CSF, GM-CSF, and IL-3 in seven-day cultures. Here both GM-CSF and IL-3 amplified total CFC that had similar multipotential colony-forming capability in either factor. G-CSF, on the other hand, depleted IL-3-responsive colony-forming cells dramatically, apparently by causing these cells to mature into granulocytes. The data suggest that a large proportion of IL-3- responsive cells in human bone marrow express receptors for G-CSF and can respond to this factor, the majority becoming neutrophils. Furthermore, the CFC maintained for 21 days in IL-3 may be a functionally distinct population from that produced after seven days culture of bone marrow cells in either IL-3 or GM-CSF.


Author(s):  
Kanive Parashiva Guruprasad ◽  
Advait Subramanian ◽  
Vikram Jeet Singh ◽  
Raghavendra Sudheer Kumar Sharma ◽  
Puthiya Mundyat Gopinath ◽  
...  

2005 ◽  
Vol 26 (4) ◽  
pp. 469-476 ◽  
Author(s):  
Xiao-lei SHI ◽  
Yu-dong QIU ◽  
Qiang LI ◽  
Ting XIE ◽  
Zhang-hua ZHU ◽  
...  

1991 ◽  
Vol 18 (3) ◽  
pp. 168-183 ◽  
Author(s):  
Marcia D. Phillips ◽  
Bruce Nascimbeni ◽  
Raymond R. Tice ◽  
Michael D. Shelby ◽  
A. A. Van Zeeland

2010 ◽  
Vol 135 ◽  
pp. S32
Author(s):  
Patricia Taylor ◽  
Gary Koski ◽  
Erin Bailey ◽  
Daniel Zimmerman ◽  
Ken S. Rosenthal

1990 ◽  
Vol 240 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Kimiko Fujie ◽  
Junko Nishi ◽  
Mieko Wada ◽  
Sakan Maeda ◽  
Taketoshi Sugiyama

2005 ◽  
Vol 74 (3) ◽  
pp. 566-572 ◽  
Author(s):  
N. Velazquez-Guadarrama ◽  
E. Madrigal-Bujaidar ◽  
D. Molina ◽  
G. Chamorro

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