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N Solvason

Publications and source records attributed to N Solvason.

7 recordsLinked to original sources
PubMed1992

The fetal omentum in mice and humans. A site enriched for precursors of CD5 B cells early in development.

From these studies the fetal omentum appears to be an important site of B-cell generation in humans and a source of CD5 B cells in mice. We have analyzed the fetal omentum in other species and have found that B-cell development as determined by the presence of cytoplasmic IgM+ pre-B cells is also detected in the fetal rabbit omentum. We do not know if there is bias towards the production of CD5 B cells in this species; however, these preliminary results demonstrate that this site may be conserved throughout evolution in mammals as a site of B-cell generation. Because the fetal liver is also a source of precursors that can reconstitute this B-cell subset, what is the relationship between omentum and liver during the development of Ly-1 B cells? The most obvious relationship between these two sites is that cells simply migrate from one location to the other; that is, precursor cells may migrate from the fetal liver into the fetal omentum and in this milieu give rise to exclusively Ly-1+ B cells or the sister population. Alternatively, precursors of Ly-1 B cells may arise in the omentum and migrate to the liver. This is demonstrated graphically in the diagram (Fig. 6a) of a transverse section through an 8-week human fetus. In this paper, however, we suggest a model for the development of Ly-1+ B cells from the omentum and liver in which Ly-1 B cells arise from distinct precursors located in situ in the mesodermally derived omentum and mesothelial-derived liver capsule. The omentum primordia forms as the back to back fusion of the mesodermally derived lining of the peritoneal cavity, and this lining surrounds the developing gut when the liver begins to develop as an outgrowth of the intestinal primordia at approximately 3.5 weeks gestation; the outer covering or capsule of the liver is derived from the same tissue of origin as the omentum. Figure 6B is a diagram of a section through the same plane as Figure 6A but the body wall has been omitted. We propose that the Ly-1+ B cells arise in situ in the omentum and lining of the liver as indicated in Figure 6B. That Ly-1+ B cells arise from distinct precursors has been suggested by others, but ours is the first evidence for a developmental site that apparently contains B-cell progenitors for this B-cell subset.

Animals↗
PubMed1992

The human fetal omentum: a site of B cell generation.

The fetal mouse omentum has been shown to be a source of precursors that exclusively reconstitutes Ly1+ B cells and the closely related Ly1- sister population, but not conventional B cells or T cells. We have extended these studies to compare B cell development in the human fetal omentum, liver, and spleen, and to demonstrate that the pro/pre-B cell compartment (CD24+, sIgM-) is detected in the omentum and liver but not spleen as early as 8 wk of gestation. From 8 to 12 wk of gestation, the proportions of IgM+ cells that were pre-B cells (cIgM+/sIgM-) in the omentum and liver were 53 +/- 15% and 45 +/- 13%, respectively, and IgM+ cells were not detectable in the spleen. After 12 wk, the percentage of pre-B cells was unchanged in the fetal liver (41 +/- 10%) but decreased significantly in the omentum (25 +/- 14%); pre-B cells were now detected in the spleen but at much lower percentages (2 +/- 3%) than either the omentum or liver. The nuclear enzyme, Tdt, was detected in approximately 25% of the CD24+ cells in the omentum and liver during the 8-12-wk time period, however, Tdt+ cells were not detected in the spleen. Approximately 40% of the mature B cells found in the omentum and spleen were CD5+ compared with only 20% in the liver. These results demonstrate that the fetal omentum, like the fetal liver and bone marrow, is a primary site of B cell development.

Antibodies, Monoclonal↗
PubMed1992

Development and function of the early B cell repertoire.

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 VH gene 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 JH gene segments in the absence of N region addition. As previously described, the most D proximal VH genes 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 VH gene, VH81X. These antibodies and another example from the VH7183 family have a broad multireactivity pattern possibly because of the presence of an unusually high number of charged amino acid groups present in the VH region. 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 VH gene 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 VHDJH genes and DJH joins. 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.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

An embryonic source of Ly1 but not conventional B cells.

Ly1+ B cells differ from conventional B cells with respect to their anatomical localization, cell surface marker expression, and antibody repertoire suggesting that they may constitute a functionally distinct subset of B cells. To determine whether Ly1+ B cells also have a developmentally distinct site of origin we grafted various fetal primordia into adult severe combined immunodeficient (scid) mice and analyzed their potential to give rise to T and B cells. We demonstrated that fetal omentum, but not spleen or thymus grafts, reconstituted exclusively Ly1 B cells (including the Ly1 sister population) as well as a population of IgM and IgA producing plasma cells in the spleen and gut, respectively. Although thymus grafts regularly reconstituted T cells, thymus plus fetal omentum cografts gave rise to a population of Ly1+ B cells as well as T cells which were also derived from omentum. However, in neither omentum nor omentum plus thymus cografts were conventional B cells detected. These results provide the first evidence that Ly1 B cells but not conventional B cells are generated from the fetal omentum.

Animals↗