Phenotypic abnormalities of splenic and bone marrow B cells in lpr and gld mice

Elizabeth A. Reap, Monica L. Piecyk, Alyce M. Oliver, Eric S. Sobel, Thomas Waldschmidt, Philip L. Cohen, Robert A. Eisenberg

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Mice homozygous for the mutant Fas gene lpr develop generalized lymphoproliferation and produce autoantibodies resembling those found in human SLE. We have previously shown that these autoantibodies are produced by B2 cells rather than B1 cells and that the autoantibody-producing B cells are intrinsically abnormal. We investigated further the lpr B cell with a large panel of antibodies to B-cell surface markers to identify phenotypic abnormalities, B cells from spleen and bone marrow of age-matched congenic mice differing only at the lpr locus were examined by flow cytometry. Two consistent phenotypic differences were identified. First, spleen cells from older lpr mice had an increase in the number and percentage of IgM+ B cells expressing low levels of CD23. Second, lpr bone marrow had decreased numbers of B220(h1) IgM+-syndecan-1+CD23+ B cells. All other markers tested, except the previously identified modest increase of Ia on lpr spleen cells, showed no consistent differences. E cells from gld mice showed the same phenotypic abnormalities as those from lpr. Compared to T cells, the relative paucity of cell surface marker differences between lpr and +/+ B cells suggests that B cells may have fewer regulatory mechanisms to silence autoreactive specificities. The phenotypic differences identified may provide clues to the mechanism of autoantibody production in lpr mice, while the overwhelming phenotypic similarity between lpr and +/+ B cells suggests that the major abnormality of lpr B cells may lie in their specificity, that is, in their inability to delete autoreactive subsets.

Original languageEnglish (US)
Pages (from-to)21-29
Number of pages9
JournalClinical Immunology and Immunopathology
Volume78
Issue number1
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Fingerprint

Bone Marrow Cells
B-Lymphocytes
Autoantibodies
Spleen
Immunoglobulin M
Bone Marrow
Syndecan-1
Congenic Mice
Flow Cytometry
T-Lymphocytes
Antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology

Cite this

Reap, E. A., Piecyk, M. L., Oliver, A. M., Sobel, E. S., Waldschmidt, T., Cohen, P. L., & Eisenberg, R. A. (1996). Phenotypic abnormalities of splenic and bone marrow B cells in lpr and gld mice. Clinical Immunology and Immunopathology, 78(1), 21-29. https://doi.org/10.1006/clin.1996.0004

Phenotypic abnormalities of splenic and bone marrow B cells in lpr and gld mice. / Reap, Elizabeth A.; Piecyk, Monica L.; Oliver, Alyce M.; Sobel, Eric S.; Waldschmidt, Thomas; Cohen, Philip L.; Eisenberg, Robert A.

In: Clinical Immunology and Immunopathology, Vol. 78, No. 1, 01.01.1996, p. 21-29.

Research output: Contribution to journalArticle

Reap, EA, Piecyk, ML, Oliver, AM, Sobel, ES, Waldschmidt, T, Cohen, PL & Eisenberg, RA 1996, 'Phenotypic abnormalities of splenic and bone marrow B cells in lpr and gld mice', Clinical Immunology and Immunopathology, vol. 78, no. 1, pp. 21-29. https://doi.org/10.1006/clin.1996.0004
Reap, Elizabeth A. ; Piecyk, Monica L. ; Oliver, Alyce M. ; Sobel, Eric S. ; Waldschmidt, Thomas ; Cohen, Philip L. ; Eisenberg, Robert A. / Phenotypic abnormalities of splenic and bone marrow B cells in lpr and gld mice. In: Clinical Immunology and Immunopathology. 1996 ; Vol. 78, No. 1. pp. 21-29.
@article{d90c70e1b3ce456abdfa03ecff4125e7,
title = "Phenotypic abnormalities of splenic and bone marrow B cells in lpr and gld mice",
abstract = "Mice homozygous for the mutant Fas gene lpr develop generalized lymphoproliferation and produce autoantibodies resembling those found in human SLE. We have previously shown that these autoantibodies are produced by B2 cells rather than B1 cells and that the autoantibody-producing B cells are intrinsically abnormal. We investigated further the lpr B cell with a large panel of antibodies to B-cell surface markers to identify phenotypic abnormalities, B cells from spleen and bone marrow of age-matched congenic mice differing only at the lpr locus were examined by flow cytometry. Two consistent phenotypic differences were identified. First, spleen cells from older lpr mice had an increase in the number and percentage of IgM+ B cells expressing low levels of CD23. Second, lpr bone marrow had decreased numbers of B220(h1) IgM+-syndecan-1+CD23+ B cells. All other markers tested, except the previously identified modest increase of Ia on lpr spleen cells, showed no consistent differences. E cells from gld mice showed the same phenotypic abnormalities as those from lpr. Compared to T cells, the relative paucity of cell surface marker differences between lpr and +/+ B cells suggests that B cells may have fewer regulatory mechanisms to silence autoreactive specificities. The phenotypic differences identified may provide clues to the mechanism of autoantibody production in lpr mice, while the overwhelming phenotypic similarity between lpr and +/+ B cells suggests that the major abnormality of lpr B cells may lie in their specificity, that is, in their inability to delete autoreactive subsets.",
author = "Reap, {Elizabeth A.} and Piecyk, {Monica L.} and Oliver, {Alyce M.} and Sobel, {Eric S.} and Thomas Waldschmidt and Cohen, {Philip L.} and Eisenberg, {Robert A.}",
year = "1996",
month = "1",
day = "1",
doi = "10.1006/clin.1996.0004",
language = "English (US)",
volume = "78",
pages = "21--29",
journal = "Clinical Immunology",
issn = "1521-6616",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Phenotypic abnormalities of splenic and bone marrow B cells in lpr and gld mice

AU - Reap, Elizabeth A.

AU - Piecyk, Monica L.

AU - Oliver, Alyce M.

AU - Sobel, Eric S.

AU - Waldschmidt, Thomas

AU - Cohen, Philip L.

AU - Eisenberg, Robert A.

PY - 1996/1/1

Y1 - 1996/1/1

N2 - Mice homozygous for the mutant Fas gene lpr develop generalized lymphoproliferation and produce autoantibodies resembling those found in human SLE. We have previously shown that these autoantibodies are produced by B2 cells rather than B1 cells and that the autoantibody-producing B cells are intrinsically abnormal. We investigated further the lpr B cell with a large panel of antibodies to B-cell surface markers to identify phenotypic abnormalities, B cells from spleen and bone marrow of age-matched congenic mice differing only at the lpr locus were examined by flow cytometry. Two consistent phenotypic differences were identified. First, spleen cells from older lpr mice had an increase in the number and percentage of IgM+ B cells expressing low levels of CD23. Second, lpr bone marrow had decreased numbers of B220(h1) IgM+-syndecan-1+CD23+ B cells. All other markers tested, except the previously identified modest increase of Ia on lpr spleen cells, showed no consistent differences. E cells from gld mice showed the same phenotypic abnormalities as those from lpr. Compared to T cells, the relative paucity of cell surface marker differences between lpr and +/+ B cells suggests that B cells may have fewer regulatory mechanisms to silence autoreactive specificities. The phenotypic differences identified may provide clues to the mechanism of autoantibody production in lpr mice, while the overwhelming phenotypic similarity between lpr and +/+ B cells suggests that the major abnormality of lpr B cells may lie in their specificity, that is, in their inability to delete autoreactive subsets.

AB - Mice homozygous for the mutant Fas gene lpr develop generalized lymphoproliferation and produce autoantibodies resembling those found in human SLE. We have previously shown that these autoantibodies are produced by B2 cells rather than B1 cells and that the autoantibody-producing B cells are intrinsically abnormal. We investigated further the lpr B cell with a large panel of antibodies to B-cell surface markers to identify phenotypic abnormalities, B cells from spleen and bone marrow of age-matched congenic mice differing only at the lpr locus were examined by flow cytometry. Two consistent phenotypic differences were identified. First, spleen cells from older lpr mice had an increase in the number and percentage of IgM+ B cells expressing low levels of CD23. Second, lpr bone marrow had decreased numbers of B220(h1) IgM+-syndecan-1+CD23+ B cells. All other markers tested, except the previously identified modest increase of Ia on lpr spleen cells, showed no consistent differences. E cells from gld mice showed the same phenotypic abnormalities as those from lpr. Compared to T cells, the relative paucity of cell surface marker differences between lpr and +/+ B cells suggests that B cells may have fewer regulatory mechanisms to silence autoreactive specificities. The phenotypic differences identified may provide clues to the mechanism of autoantibody production in lpr mice, while the overwhelming phenotypic similarity between lpr and +/+ B cells suggests that the major abnormality of lpr B cells may lie in their specificity, that is, in their inability to delete autoreactive subsets.

UR - http://www.scopus.com/inward/record.url?scp=0029970275&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029970275&partnerID=8YFLogxK

U2 - 10.1006/clin.1996.0004

DO - 10.1006/clin.1996.0004

M3 - Article

VL - 78

SP - 21

EP - 29

JO - Clinical Immunology

JF - Clinical Immunology

SN - 1521-6616

IS - 1

ER -