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B Cell Heterogeneity

I. A Study of B Cell Subpopulations Involved in the Reconstitution of an X-Linked Immune Defect of B Cell Differentiation

From the Departments of Pediatrics and Committee on Immunology, the University of Chicago, and La Rabida Children's Hospital and Research Center, Chicago, Illinois 60649

Abstract

Male (CBA/N x BALB/c) F₁ hybrid mice cannot mount humoral immune responses to thymus-dependent (T.D.) or thymus-independent (T.I.) phosphorylcholine (PC) antigens and to trinitrophenyl (TNP)-AECM-Ficoll and TNP-AECM-dextran. Transplantation of spleen, bone marrow, or neonatal liver cells from BALB/c mice can restore responsiveness to these antigens. Engraftment of spleen and bone marrow cells occurs in unirradiated NBF₁ hosts, whereas restoration of PFC responses by neonatal liver cells requires a sublethally irradiated NBF₁ recipient. Reconstitution experiments demonstrated that the spleen contains T.D. and T.I. B cell precursors that can respond immediately to antigenic challenge, although the bone marrow contains only mature T.D. B cells and immature cells (progenitor cells) which will restore T.I. responses 2 weeks after transplantation. Neonatal liver cells contain only immature progenitor cells which, after 1 to 2 weeks in the NBF₁ recipient, become antigen-reactive cells. In contrast to anti-TNP PFC responses, which are fully restored in all NBF₁ recipients of BALB/c neonatal cells, only a fraction of NBF₁ mice gain responsiveness to PC antigens. The frequency of successful reconstitutions of T.D. anti-PC PFC responses was higher than T.I. anti-PC responses. Idiotypic analysis in the reconstituted recipients demonstrated that H8 and non-H8 anti-PC PFC were being generated. Evidence is presented to indicate that the reconstitution with neonatal liver cells functionally resembles a limiting dilution assay for immature PC-specific progenitor cells, which include both H8 and non-H8 idiotype specificities in T.D. and T.I. anti-PC responses.

Footnotes

¹ Supported by a Basil O'Connor Research Starter Grant from the National Foundation March of Dimes and by National Institutes of Health Grant 1-R01-A1-14530-01. Recipient of Research Career Development Award 1-K04-A1-00268-01.

² Supported by National Institutes of Health Grant 1-R01-A1-14530-01.

³ Supported by the Francis L. Lederer Fellowship and United States Public Health Service Grant A1-10242.

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				J. Rohrer and M. E. Conley Correction of X-Linked Immunodeficient Mice by Competitive Reconstitution With Limiting Numbers of Normal Bone Marrow Cells Blood, November 15, 1999; 94(10): 3358 - 3365. [Abstract] [Full Text] [PDF]