摘要:

In an attempt to elucidate the possible role of cytokines in autocrine growth of Ly-1 + B cells, and the role of this subset of B cells in immune regulation, both in normal and diseased hosts, we have performed a systematic analysis of cytokine production by a series of mouse Ly-1+B lymphomas, as well as normal peritoneal Ly-1+and conventional B cells. The lymphomas all express TGF-β, and some express IL-3 and IL-4. We observed that both the lymphomas and the peritoneal cells produce TNF-α, TNF-βand IL-6. Another cytokine, IL-10, is produced predominantly by peritoneal Ly-1+B cells from healthy mice and by Ly-1+B lymphomas, but not by conventional B cells. As IL-10 regulates the production of monokines and a subset of T-cell derived cytokines, our results suggest a broad immunoregulatory role for Ly-1 B cells. To complement these studies we have also examined the responses of Ly-1 B cells to mitogens and cytokines previously shown to stimulate conventional B cells. In summary, Ly-1 B cells, in contrast to conventional B cells do not respond to anti-Ig antibodies, even in the presence of IL-4. They do respond to LPS, and this response is preferentially enhanced by IL-5, and marginally enhanced by IL-3. Surprisingly LPS-induced proliferation of peritoneal B cells is inhibited by IL-6 and to a greater extent by IL-10. Whether this inhibition is a result of differentiation into Ig secreting cells is currently being evaluated. We discuss our findings in terms of the potential of Ly-1 B cells to regulate their own development and the immunocompetence of other cells.

ISSN:0883-0185    

DOI:10.3109/08830189209055575

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

A unifying theory of B cell development and lineage commitment is presented. There are two firmly established B lineages: cells which normally arise only from fetal sources and lack N insertions in their rearranged heavy chains; and N-containing cells which arise from adult bone marrow precursors (and perhaps from late fetal sources). Commitment to the expression of CD5 and the capacity for long-life (or self-renewal) are induced as a consequence of sIg cross-linking, typically by a repeating epitope, thymus independent type two antigen. Alternatively, activation resulting from cognate interaction with a helper T cell does not induce CD5 but results in lower expression of J11d. In this case activation occurs in the absence of sIg cross-linking. It is further proposed that differences in the Ig repertoire make it highly likely that fetal/neonatal, but not adult derived B cells will be induced to express CD5. The model offers a plausible explanation for the correlation of CD5 expression and natural autoantibody production by neonatal B cells. Possible sources of pathogenic autoantibody are discussed in the context of this model.

ISSN:0883-0185    

DOI:10.3109/08830189209055576

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The early B cell repertoire is characterized by extensive interconnectivity, autoreactivity and multispecificity. Our preliminary sequence analysis of some of the idiotype specific antibodies is beginning to provide molecular clues to explain the observed multireactivity and the expression of shared idiotypic determinants on immunoglobulins of early B cells. The VHgene rearrangements analyzed are typical of the early pre-B cell and CD5 B cell repertoire. Some of these include shared or identical CDR3 regions resulting from the use of germline VH, D and JHgene segments in the absence of N region addition. As previously described, the most D proximal VHgenes are also used most frequently. Collectively these genetic restrictions, together with the lack of somatic mutation, suggest that the characteristic self reactivity of the early B cell repertoire is related to the expression of germline gene segments and limited use of diversification mechanisms. It has also been possible for the first time to isolate hybridomas secreting functional IgM molecules which use the most D proximal VHgene, VH81X. These antibodies and another example from theH7183 family have a broad multireactivity pattern possibly because of the presence of an unusually high number of charged amino acid groups present in the VHregion. These findings are preliminary and more extensive studies are needed to establish if these groups are responsible for the highly cross-reactive nature of these antibodies. Nevertheless, these unusual characteristics signify a unique role for antibodies expressing this VHgene during B cell development. It is also clear that the observed anti-lymphocyte reactivity, another feature of the newborn repertoire, is the result of the prevalence of B cells using similar if not identical VHDJHgenes and DJHjoins. The development of these B cells appears to occur consistently in early ontogeny and, again, are not found in conventional splenic B cells obtained from the normal adult. Understanding the functional significance of the early appearance of these antibodies may help to clarify and understand their role during development as well as in autoimmunity.We propose that the unique self reactive nature of the early repertoire provides a pattern within which self-assertiveness develops and results in the establishment of the adult repertoire. In doing so, dominant clones are established which may or may not be within, but whose selection and differentiation is directed by the CD5 B cell subset. Further understanding of how these interactions occur will come only from deeper understanding of the molecular nature of these receptors and their target self or non-self antigens.

ISSN:0883-0185    

DOI:10.3109/08830189209055577

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189209055578

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189209055564

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor