Abstract
Sepharose-anti-Ig and purified populations of small, high-density B cells have been used to study the formation and function of B lymphoblasts. Sepharose-anti-Ig converts small, Ia-poor B cells with a high-buoyant density to large, Ia-rich, B blasts with a low-buoyant density. We find that this response proceeds efficiently in the absence of IL-4 (BSF-1) as well as most T cells, macrophages, and dendritic cells. Further development of the blasts requires an additional stimulus, such as LPS or the conditioned medium of stimulated EL-4 thymoma cells. Within 6 h, blasts begin to enter S phase and within 24 h most divide. At later times (48-72 h) most of the blasts are actively secreting IgM. Recombinant IL-1, -2, -3, and -4 have little or no effect on the B blasts, and a neutralizing mAb to IL-4 does not block the response to EL-4 Sn. We conclude that Sepharose-anti-Ig induces B cell blastogenesis in a T-independent fashion and that these blasts represent a highly enriched population of cells that respond to distinct, T cell-derived lymphokines.
Full Text
The Full Text of this article is available as a PDF (857.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anderson J., Melchers F. T cell-dependent activation of resting B cells: requirement for both nonspecific unrestricted and antigen-specific Ia-restricted soluble factors. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2497–2501. doi: 10.1073/pnas.78.4.2497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeFranco A. L., Raveche E. S., Paul W. E. Separate control of B lymphocyte early activation and proliferation in response to anti-IgM antibodies. J Immunol. 1985 Jul;135(1):87–94. [PubMed] [Google Scholar]
- Defranco A. L., Raveche E. S., Asofsky R., Paul W. E. Frequency of B lymphocytes responsive to anti-immunoglobulin. J Exp Med. 1982 May 1;155(5):1523–1536. doi: 10.1084/jem.155.5.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Howard M., Farrar J., Hilfiker M., Johnson B., Takatsu K., Hamaoka T., Paul W. E. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982 Mar 1;155(3):914–923. doi: 10.1084/jem.155.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Howard M., Mizel S. B., Lachman L., Ansel J., Johnson B., Paul W. E. Role of interleukin 1 in anti-immunoglobulin-induced B cell proliferation. J Exp Med. 1983 May 1;157(5):1529–1543. doi: 10.1084/jem.157.5.1529. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Howard M., Paul W. E. Regulation of B-cell growth and differentiation by soluble factors. Annu Rev Immunol. 1983;1:307–333. doi: 10.1146/annurev.iy.01.040183.001515. [DOI] [PubMed] [Google Scholar]
- Inaba K., Witmer M. D., Steinman R. M. Clustering of dendritic cells, helper T lymphocytes, and histocompatible B cells during primary antibody responses in vitro. J Exp Med. 1984 Sep 1;160(3):858–876. doi: 10.1084/jem.160.3.858. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Isakson P. C. Antiimmunoglobulin-treated B cells respond to a B cell differentiation factor for IgG1. J Exp Med. 1986 Jul 1;164(1):303–308. doi: 10.1084/jem.164.1.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Isakson P. C., Puré E., Vitetta E. S., Krammer P. H. T cell-derived B cell differentiation factor(s). Effect on the isotype switch of murine B cells. J Exp Med. 1982 Mar 1;155(3):734–748. doi: 10.1084/jem.155.3.734. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kishimoto T., Miyake T., Nishizawa Y., Watanabe T., Yamamura Y. Triggering mechanism of B lymphocytes. I. Effect of anti-immunoglobulin and enhancing soluble factor on differentiation and proliferation of B cells. J Immunol. 1975 Nov;115(5):1179–1184. [PubMed] [Google Scholar]
- Layton J. E., Krammer P. H., Hamaoka T., Uhr J. W., Vitetta E. S. Small and large B cells respond differently to T cell-derived B cell growth and differentiation factors. J Mol Cell Immunol. 1985;2(3):155–167. [PubMed] [Google Scholar]
- Ly I. A., Mishell R. I. Separation of mouse spleen cells by passage through columns of sephadex G-10. J Immunol Methods. 1974 Aug;5(3):239–247. doi: 10.1016/0022-1759(74)90108-2. [DOI] [PubMed] [Google Scholar]
- Melchers F., Lernhardt W. Three restriction points in the cell cycle of activated murine B lymphocytes. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7681–7685. doi: 10.1073/pnas.82.22.7681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mond J. J., Finkelman F. D., Sarma C., Ohara J., Serrate S. Recombinant interferon-gamma inhibits the B cell proliferative response stimulated by soluble but not by Sepharose-bound anti-immunoglobulin antibody. J Immunol. 1985 Oct;135(4):2513–2517. [PubMed] [Google Scholar]
- Müller W., Kühn R., Goldmann W., Tesch H., Smith F. I., Radbruch A., Rajewsky K. Signal requirements for growth and differentiation of activated murine B lymphocytes. J Immunol. 1985 Aug;135(2):1213–1219. [PubMed] [Google Scholar]
- O'Garra A., Warren D. J., Holman M., Popham A. M., Sanderson C. J., Klaus G. G. Interleukin 4 (B-cell growth factor II/eosinophil differentiation factor) is a mitogen and differentiation factor for preactivated murine B lymphocytes. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5228–5232. doi: 10.1073/pnas.83.14.5228. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ohara J., Paul W. E. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. doi: 10.1038/315333a0. [DOI] [PubMed] [Google Scholar]
- Parker D. C., Fothergill J. J., Wadsworth D. C. B lymphocyte activation by insoluble anti-immunoglobulin: induction of immunoglobulin secretion by a T cell-dependent soluble factor. J Immunol. 1979 Aug;123(2):931–941. [PubMed] [Google Scholar]
- Pure E., Isakson P. C., Kappler J. W., Marrack P., Krammer P. H., Vitetta E. S. T cell-derived B cell growth and differentiation factors. Dichotomy between the responsiveness of B cells from adult and neonatal mice. J Exp Med. 1983 Feb 1;157(2):600–612. doi: 10.1084/jem.157.2.600. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rabin E. M., Mond J. J., Ohara J., Paul W. E. B cell stimulatory factor 1 (BSF-1) prepares resting B cells to enter S phase in response to anti-IgM and lipopolysaccharide. J Exp Med. 1986 Aug 1;164(2):517–531. doi: 10.1084/jem.164.2.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rabin E. M., Ohara J., Paul W. E. B-cell stimulatory factor 1 activates resting B cells. Proc Natl Acad Sci U S A. 1985 May;82(9):2935–2939. doi: 10.1073/pnas.82.9.2935. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Simpson L. G., Isakson P. C. Role of DNA synthesis in secretion of immunoglobulin from murine B cells stimulated by T cell derived lymphokines. J Immunol. 1986 Sep 15;137(6):1797–1802. [PubMed] [Google Scholar]
- Steinman R. M., Nogueira N., Witmer M. D., Tydings J. D., Mellman I. S. Lymphokine enhances the expression and synthesis of Ia antigens on cultured mouse peritoneal macrophages. J Exp Med. 1980 Nov 1;152(5):1248–1261. doi: 10.1084/jem.152.5.1248. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swain S. L., Dutton R. W. Production of a B cell growth-promoting activity, (DL)BCGF, from a cloned T cell line and its assay on the BCL1 B cell tumor. J Exp Med. 1982 Dec 1;156(6):1821–1834. doi: 10.1084/jem.156.6.1821. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swain S. L., Howard M., Kappler J., Marrack P., Watson J., Booth R., Wetzel G. D., Dutton R. W. Evidence for two distinct classes of murine B cell growth factors with activities in different functional assays. J Exp Med. 1983 Sep 1;158(3):822–835. doi: 10.1084/jem.158.3.822. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swain S. L., Howard M., Kappler J., Marrack P., Watson J., Booth R., Wetzel G. D., Dutton R. W. Evidence for two distinct classes of murine B cell growth factors with activities in different functional assays. J Exp Med. 1983 Sep 1;158(3):822–835. doi: 10.1084/jem.158.3.822. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thompson C. B., Schaefer M. E., Finkelman F. D., Scher I., Farrar J., Mond J. J. T cell-derived B cell growth factor(s) can induce stimulation of both resting and activated B cells. J Immunol. 1985 Jan;134(1):369–374. [PubMed] [Google Scholar]
- Thompson C. B., Scher I., Schaefer M. E., Lindsten T., Finkelman F. D., Mond J. J. Size-dependent B lymphocyte subpopulations: relationship of cell volume to surface phenotype, cell cycle, proliferative response, and requirements for antibody production to TNP-Ficoll and TNP-BA. J Immunol. 1984 Nov;133(5):2333–2342. [PubMed] [Google Scholar]
- Vitetta E. S., Ohara J., Myers C. D., Layton J. E., Krammer P. H., Paul W. E. Serological, biochemical, and functional identity of B cell-stimulatory factor 1 and B cell differentiation factor for IgG1. J Exp Med. 1985 Nov 1;162(5):1726–1731. doi: 10.1084/jem.162.5.1726. [DOI] [PMC free article] [PubMed] [Google Scholar]
