Expression of phosphorylcholine-specific B cells during murine development

Sigal, Nolan H.; Pickard, Allan R.; Metcalf, Eleanor S.; Gearhart, Patricia J.; Klinman, Norman R.

doi:10.1084/jem.146.4.933

Cited by 81 publications

(50 citation statements)

References 47 publications

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“…Although the B cell specificity repertoire of adult individuals is extraordinarily diverse, inbred murine strains reproducibly display certain clonotypes at a relatively high frequency (1)(2)(3)(4)(5)(6)(7)(8)(9). Often such clonotypes dominate the in vivo and in vitro response to given antigens.…”

mentioning

confidence: 99%

“…Often such clonotypes dominate the in vivo and in vitro response to given antigens. The response to phosphorylcholine (PC) ~ of BALB/c mice is one such response, wherein the repertoire of responsive clonotypes includes over 100 distinct specificities (10,11), yet one clonotype, that which is indistinguishable from the TEPC-15 (T 15) myeloma protein, represents the majority of the response (5)(6)(7)(8)(9)(10)(11). The basis for such clonai dominance within an immune response is not yet fully understood.…”

mentioning

confidence: 99%

“…The basis for such clonai dominance within an immune response is not yet fully understood. In the case of the T 15 response in BALB/c mice, it has been found that B cells expressing this clonotype are present in high frequency in the spleen before immunization (7)(8)(9), which could, in part, account for its dominance within the response to PC. However, the mechanism responsible for the high frequency of expression of this clonotype and the low frequency of expression of the vast majority of other clonotypes has yet to be determined.…”

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confidence: 99%

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Role of variable region gene expression and environmental selection in determining the antiphosphorylcholine B cell repertoire.

Stone¹

1983

The Journal of Experimental Medicine

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To evaluate the role of environmental selective processes, as opposed to variable region gene expression, in the determination of B cell repertoire expression, we have assessed the phosphorylcholine (PC)-specific repertoire of precursor cells that remain in bone marrow cell populations after the removal of surface immunoglobulin (sIg)-bearing cells. Such cells are assumed to represent a stage in B cell maturation before the expression of sIg, and thus at a time when they have not as yet interfaced with environmental influences that operate through sIg receptors such as antigenic stimulation, tolerance, or antiidiotypic regulation. The repertoire as expressed in these cells, therefore, should reflect the readout of immunoglobulin variable region genes as they are expressed in progenitors to B cells. The results of these studies indicate that, as in mature primary B cell pools of BALB/c mice, the majority of PC-responsive sIg- bone marrow cells are of the T15 clonotype. Thus, environmental selective mechanisms would not appear to be required for the high frequency of B cells of the T15 idiotype in the primary B cell repertoire of BALB/c mice. Analysis of the sIg- bone marrow cells in (CBA/N X BALB/c)F1 male mice demonstrated that the deficit of PC-responsive mature B cells, which is a characteristic of this murine strain, must occur after receptor expression, since a normal frequency of PC-responsive and T15-expressing cells is present in their sIg- bone marrow population. Finally, these same mice were used to obtain bone marrow cell preparations from individual leg bones, so as to permit an analysis of the occurrence of T15+ and T15- clonotypes within individual bone marrow populations. The findings from these studies indicate that T15+ B cells occur as a high frequency event within bone marrow generative cell pools. Furthermore, bone marrow populations that are positive for PC-responsive precursor cells often display multiple copies of such precursor cells that are exclusively either T15+ or T15-. This finding indicates that clonal expansion of cells within the B cell lineage apparently occurs before immunoglobulin receptor acquisition.

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Role of variable region gene expression and environmental selection in determining the antiphosphorylcholine B cell repertoire.

Stone¹

1983

The Journal of Experimental Medicine

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“…This is in contrast to specificities directed against other haptens such as phosphorylcholine, which develop later in ontogeny (22). From these results Klinman and Press (21) predicted that the DNP clonotypes would be expressed as early as the 15th d of gestation in fetal spleen.…”

Section: Discussionmentioning

confidence: 96%

“…Considerable evidence indicates that there is a sequential appearance of various specificities or clonotypes (22,26,27), and day 18 or 19 may mark the appearance of many later-developing, non-DNP specificities.…”

Section: Discussionmentioning

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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The lack of compensatory increases of cells producing anti‐phosphorylcholine antibodies bearing other idiotypes in TEPC‐15 idiotype‐suppressed inbred and outbred mice

Kim

Benewicz

1980

Eur J Immunol

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Idiotype analyses of plaque-forming cells using anti-idiotype antibody against TEPC-15 myeloma protein (anti-T 15 id) indicated that the proportion of plaque-forming cells producing anti-phosphorylcholine (PC) antibodies with idiotypic determinants of T15 id varied depending on the strain of mice (15-97%). However, treatment of neonates of those mouse strains with the anti-T 15 id antibody rendered them unresponsive to subsequent stimulation with PC-containing antigen (less than 7% of control response). The treatment of spleen cell cultures, derived from adult mice, with anti-T 15 id antibody resulted in complete suppression of T 15 id, although the suppression of the total anti-PC response was much less pronounced as compared to that induced in vivo. These results suggest that anti-T 15 id antibodies injected in the neonatal period may chronically inhibit the differentiation of B lymphocytes specific for PC. The lack of compensatory increases in the production of anti-PC antibodies bearing other idiotypes in T 15 id-suppressed mice does not appear to be related to the clonal proportion of cells producing anti-PC with non-T 15 id. This tolerance induction by anti-idiotype antibody appears to be unique to the nature of clonal differentiation of anti-PC-producing lymphocytes.

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Expression of phosphorylcholine-specific B cells during murine development

Cited by 81 publications

References 47 publications

Role of variable region gene expression and environmental selection in determining the antiphosphorylcholine B cell repertoire.

Role of variable region gene expression and environmental selection in determining the antiphosphorylcholine B cell repertoire.

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

The lack of compensatory increases of cells producing anti‐phosphorylcholine antibodies bearing other idiotypes in TEPC‐15 idiotype‐suppressed inbred and outbred mice

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