Current Problem Areas in the Study of B Lymphocyte Differentiation

Nossal, G. J. V.; Shortman, Ken; Howard, Maureen; Pike, Beverley L.

doi:10.1111/j.1600-065x.1977.tb00250.x

Cited by 28 publications

(8 citation statements)

References 25 publications

(17 reference statements)

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“…This view is supported by the similarity in the biological and kinetic properties of marrow lymphocytes and of virgin B lymphocytes, as defined by functional assays. Thus, many virgin B lymphocytes in the spleen are small cells (11,31,32), newly formed from proliferating precursors (11,28) and having a short functional one halflife (33). The marrow itself contains few cells immediately responsive to primary antigens (27,(29)(30)(31), but such cells rapidly appear when marrow cells are either cultured (29,30) or transferred to adoptive hosts before antigenic challenge (29).…”

Section: Maturation Of Newly Formed Marrow Derived Small Lymphocytesmentioning

confidence: 99%

Maturation of bone marrow lymphocytes. II. Development of Fc and complement receptors and surface immunoglobulin studied by rosetting and radioautography.

Yang¹,

Miller²,

Osmond³

1978

The Journal of Experimental Medicine

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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.

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Section: Maturation Of Newly Formed Marrow Derived Small Lymphocytesmentioning

confidence: 99%

Maturation of bone marrow lymphocytes. II. Development of Fc and complement receptors and surface immunoglobulin studied by rosetting and radioautography.

Yang¹,

Miller²,

Osmond³

1978

The Journal of Experimental Medicine

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“…However, recent experiments have strongly implicated antibodies produced by sensitised B cells as responsible for the adoptive transfer of immunity to B. microti (Meeusen, Lloyd and Soulsby, 1984). Immunological studies have identified various subpopulations of B cells including the antibody-forming cell (AFC) and the B memory cell (Nossal et al, 1977). As the AFC has been implicated in the adoptive transfer of immunity to Plasmodium berghei infections in mice (Gravely and Kreier, 1976), its possible role in the protection against B. microti infections observed after the transfer of immune spleen cells was investigated.…”

Section: Introductionmentioning

confidence: 99%

BABESIA MICROTI IN MICE. SUBPOPULATIONS OF CELLS INVOLVED IN THE ADOPTIVE TRANSFER OF IMMUNITY WITH IMMUNE SPLEEN CELLS

Meeusen

Lloyd

Soulsby

1984

Aust J Exp Biol Med

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Summary Protection against a primary Babesia microti infection in mice, induced by the adoptive transfer of immune spleen cells, was abolished when the immune spleen cells were treated with mitomycin C prior to transfer. Since mitomycin C treatment prevents the replication of lymphocytes without affecting other cell functions, these results would suggest that the transferred cells required proliferation in the recipient mice before they could exert their protective effect, and this excludes the already differentiated antibody‐forming cells (AFC's), macrophages and sensitised helper T cells. This was partly supported by the finding that Sephadex G‐10 non‐adherent immune cells, depleted of macrophages and AFC's, still conferred a strong protection after transfer. However, the Sephadex G‐10 adherent cells, on a cell to cell basis, initially conferred a better protection against B. microti than did the non‐adherent cells or unfractionated immune spleen cells. The possibility of the retention of an intermediate B memory cell type on the Sephadex G‐10 columns and the suppression of antibody production are discussed in view of these results.

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“…This report then indicates that at least certain types of variants in antibody specificity are not common in clones of AFC arising in 3 4 days from the mature B cell subset we have previously termed "direct AFC progenitors" [21]. However, we have recently described an earlier Ig-positive B cell subset that we have termed a "pre-progenitor", that responds to antigen stimulation in a nonspecific way (probably via macrophage factors), by proliferating and producing direct AFC progenitor B cells [21-241.…”

Section: Discussionmentioning

confidence: 79%

Some limits to post‐antigen generation of diversity: Failure to detect variants in clones of hapten‐specific antibody‐forming cells (AFC) developing in culture from direct AFC‐progenitor B cells

et al. 1979

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A search was made for variants in clones of hapten-specific antibody-forming cells (AFC) arising by stimulation of mature B cells with either thymus-independent hapten-POL (polymerized bacterial flagellin) conjugates, or the polyclonal activator lipopolysaccharides. Enriched, hapten-binding B cells or unfractionated spleen cells were cultivated for 3-4 days at limiting dilution in the presence of thymus filler cells, and the AFC in each microculture well were then assayed for plaque formation on various hapten-sheep red cell monolayers. No variants were found from (4-hydroxy-3-iodo-5-nitrophenyl) acetyl (NIP) to 2,4-dinitrophenyl specificity, nor from fluorescein (FLU) to NIP specificity. No variants were found in avidity for FLU hapten. All 374 clones examined, including clones of up to 300 AFC, appeared to be homogeneous in antibody specificity and plaque morphology under our conditions. These results differ from published findings using erythrocytes as antigens. Reasons for this discrepancy are discussed, including differences in sensitivity differences in immunological similarity between the test antigens, and in the particular B cell subsets involved.

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Current Problem Areas in the Study of B Lymphocyte Differentiation

Cited by 28 publications

References 25 publications

Maturation of bone marrow lymphocytes. II. Development of Fc and complement receptors and surface immunoglobulin studied by rosetting and radioautography.

Maturation of bone marrow lymphocytes. II. Development of Fc and complement receptors and surface immunoglobulin studied by rosetting and radioautography.

BABESIA MICROTI IN MICE. SUBPOPULATIONS OF CELLS INVOLVED IN THE ADOPTIVE TRANSFER OF IMMUNITY WITH IMMUNE SPLEEN CELLS

Some limits to post‐antigen generation of diversity: Failure to detect variants in clones of hapten‐specific antibody‐forming cells (AFC) developing in culture from direct AFC‐progenitor B cells

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