The B Cell Specificity Repertoire: Its Relationship to Definable Subpopulations

Klinman, Norman R.; Press, Joan L.

doi:10.1111/j.1600-065x.1975.tb00165.x

Cited by 81 publications

(102 citation statements)

References 123 publications

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“…These studies were facilitated by a modification of the in vitro splenic focus technique in which fragment cultures are derived from the spleens of irradiated, carrier-primed, syngeneic adult recipients of neonatal or adult B cells. These recipient fragment cultures permit the antigenic stimulation of almost all resident transferred hapten-specific precursor cells by providing all ancillary mechanisms of stimulation (32). Furthermore, hapten-specific B-cell tolerance can be studied without the complications ofT-cell tolerance by using one hapten carrier for tolerance induction followed by challenge with the same hapten on a second carrier to which the recipient has been primed.…”

Section: Antigen Concentration and Carrier Independence Of Tolerance mentioning

confidence: 99%

“…Thereafter, the proportion of cells not susceptible to tolerance induction (adult-like B cells) constantly increases and attains adult levels by the 7th day after birth. Since the parameters of stimulation of BALB/c neonatal splenic B cells have been previously characterized (29) and the clonotypes of the majority of neonatal BALB/c cells responsive to DNP and TNP identified (30)(31)(32), it is now possible to compare precisely the parameters of tolerance induction and stimulation of these B cells. The findings show that the range of antigen concentrations capable of inducing tolerance (10 -5 M-10 -9 M haptenic determinant) closely reflects the concentrations that are optimal for the stimulation of these cells.…”

Section: Antigen Concentration and Carrier Independence Of Tolerance mentioning

confidence: 99%

“…Thus, tolerance induction or immune induction of neonatal and adult B cells can be compared at the level of individual B cells. In addition, this technique is currently the only available method that permits measurable stimulation of neonatal B cells under defined conditions and allows the characterization of the isotype and clonotype (individual antigenic specificity) of the antibody product of each stimulated B cell (29)(30)(31)(32)). …”

Section: Antigen Concentration and Carrier Independence Of Tolerance mentioning

confidence: 99%

“…Previous studies from this laboratory have demonstrated that the splenic focus technique permits detectable stimulation of individual neonatal or adult clonal precursor cells (28)(29)(30)(31)(32). Since tolerogens can be added to fragment cultures and removed before stimulation, this system provides a unique opportunity to compare the interaction of tolerogen with individual neonatal and adult cells.…”

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In vitro tolerance induction of neonatal murine B cells.

Metcalf¹,

Klinman²

1976

The Journal of Experimental Medicine

263

149

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Immunologic tolerance was originally defined as specific hyporesponsiveness to an antigen which results from prior contact with that antigen (1, 2). The concept of natural tolerance to self-antigens was perceived by Burnet (3) as the deletion of clones reactive to autologous antigens after contact of these antigens with the reactive cells' specific antigen receptors during the development of the cell's immunologic competence. If such a theory were to have physiological relevance, then several predictions should be realized: (a) developing cells should be significantly more susceptible to tolerance induction than their mature counterparts; (b) tolerance should be inducible over a wide range of antigen concentrations, since the concentrations of different self-antigens present presumably vary; (c) since the spectrum of self-antigens is diverse, the development of unresponsiveness should be plausible with a wide variety of antigenic structures; (d) since bone marrow-derived precursors to antibody-forming cells (B cells) presumably mature independently of other cell types, induction of B-cell tolerance should occur in the absence of antigen-specific thymus-derived lymphocytes (T cells); (e) the discrimination between self and nonself would be absolute, and therefore, tolerance should exhibit exquisite determinant specificity.

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Section: Antigen Concentration and Carrier Independence Of Tolerance mentioning

confidence: 99%

Section: Antigen Concentration and Carrier Independence Of Tolerance mentioning

confidence: 99%

Section: Antigen Concentration and Carrier Independence Of Tolerance mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

In vitro tolerance induction of neonatal murine B cells.

Metcalf¹,

Klinman²

1976

The Journal of Experimental Medicine

263

149

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“…This constraint has recently been removed through B-cell cloning assays, in particular, the in vitro splenic focus assay developed by Klinman and Press (10,11) in which the adult splenic environment is provided complete with carrier-primed T cells, thus facilitating the measurement of B-cell precursors in fetal and neonatal tissues. It is, therefore, of great interest to combine the technique of organ culture with this sensitive B-cell cloning assay to study the differentiation of B cells in relation to immune reactivity.…”

mentioning

confidence: 99%

Ontogenic development of B-lymphocyte function and tolerance susceptibility in vivo and in an in vitro organ culture system.

Teale¹,

Mandel²

1980

The Journal of Experimental Medicine

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The study of the development of B cells in the various lymphoid tissues in vivo is complicated by factors relating to cell migration. An in vitro organ culture system provides an opportunity for analyzing the differentiation of B lymphocytes in a closed system without the complication of cell migration. Moreover, it is possible to manipulate the experimental conditions in vitro in an attempt to alter the development of B cells and learn more about the process. One such manipulation is the addition of a tolerogen (e.g., a hapten protein conjugate) to the culture medium to study its effect on the development of hapten specific B cells.It has previously been shown that some in vitro systems can support the growth and differentiation of fetal lymphoid tissues. 6-8). Thus, the majority of studies with fetal tissues, particularly in vitro studies, have followed Bcell differentiation by the acquisition of mitogen reactivity, the development of antigen binding cells, or the acquisition of s-Ig. Although these markers do indeed reflect the maturation of B cells, they do not address the most important aspect of the B cell, namely the production of antibody to a specific antigen.In the past it has been very difficult to study the specific responses of fetal lymphoid cells or even neonatal cells because of the small number of B cells present for a

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Some design principles for immune system recognition

Perelson

Wiegel

1999

Complexity

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The B Cell Specificity Repertoire: Its Relationship to Definable Subpopulations

Cited by 81 publications

References 123 publications

In vitro tolerance induction of neonatal murine B cells.

In vitro tolerance induction of neonatal murine B cells.

Ontogenic development of B-lymphocyte function and tolerance susceptibility in vivo and in an in vitro organ culture system.

Some design principles for immune system recognition

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