Abstract
IgA memory B cells have been operationally defined as precursors that give rise to clones exclusively secreting IgA antibodies upon antigen stimulation in a T-cell dependent splenic fragment culture. B lymphocytes that are sIgA+ account for a small fraction of Peyer's patch lymphocytes, but these can be clearly divided into two subsets. One subset contains the majority of sIgA+ B cells and most of these are in S, G2, or M phase of the cell cycle. These cells are germinal center B cells, as defined by being S kappa low and peanut agglutinin (PNA)high, and contain most of the mRNA alpha. Though these germinal center cells may contain the majority of sIgA+ B cells and may contain precursors for memory cells, preplasma cells, or both, they do not appear to be immediately responsive to stimulation by antigen. Rather, the S kappa high, PNAlow subset of sIgA+ B cells, most of which are in G0 or G1 and have only low levels of mRNA alpha appear to contain most of the clonal precursors that are committed to IgA, i.e., the functional memory cells that give rise to clones exclusively secreting IgA upon stimulation with thymus-dependent antigen in the presence of T cells. There is also a population of Peyer's patch B cells that neither bears detectable sIgA nor has mRNA alpha detectable by cytoplasmic dot blotting but contains a small proportion of the functional IgA memory cells.
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- Berman J. W., Basch R. S. Amplification of the biotin-avidin immunmofluorescence technique. J Immunol Methods. 1980;36(3-4):335–338. doi: 10.1016/0022-1759(80)90138-6. [DOI] [PubMed] [Google Scholar]
- Butcher E. C., Rouse R. V., Coffman R. L., Nottenburg C. N., Hardy R. R., Weissman I. L. Surface phenotype of Peyer's patch germinal center cells: implications for the role of germinal centers in B cell differentiation. J Immunol. 1982 Dec;129(6):2698–2707. [PubMed] [Google Scholar]
- Cebra J. J., Griffin P. M., Lebman D. A., London S. D. Perturbations in Peyer's patch B cell populations indicative of priming for a secretory IgA response. Adv Exp Med Biol. 1987;216A:3–14. doi: 10.1007/978-1-4684-5344-7_2. [DOI] [PubMed] [Google Scholar]
- Coico R. F., Bhogal B. S., Thorbecke G. J. Relationship of germinal centers in lymphoid tissue to immunologic memory. VI. Transfer of B cell memory with lymph node cells fractionated according to their receptors for peanut agglutinin. J Immunol. 1983 Nov;131(5):2254–2257. [PubMed] [Google Scholar]
- Coleclough C., Cooper D., Perry R. P. Rearrangement of immunoglobulin heavy chain genes during B-lymphocyte development as revealed by studies of mouse plasmacytoma cells. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1422–1426. doi: 10.1073/pnas.77.3.1422. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cory S., Jackson J., Adams J. M. Deletions in the constant region locus can account for switches in immunoglobulin heavy chain expression. Nature. 1980 Jun 12;285(5765):450–456. doi: 10.1038/285450a0. [DOI] [PubMed] [Google Scholar]
- Craig S. W., Cebra J. J. Peyer's patches: an enriched source of precursors for IgA-producing immunocytes in the rabbit. J Exp Med. 1971 Jul 1;134(1):188–200. doi: 10.1084/jem.134.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis M. M., Calame K., Early P. W., Livant D. L., Joho R., Weissman I. L., Hood L. An immunoglobulin heavy-chain gene is formed by at least two recombinational events. Nature. 1980 Feb 21;283(5749):733–739. doi: 10.1038/283733a0. [DOI] [PubMed] [Google Scholar]
- Gearhart P. J., Cebra J. J. Differentiated B lymphocytes. Potential to express particular antibody variable and constant regions depends on site of lymphoid tissue and antigen load. J Exp Med. 1979 Jan 1;149(1):216–227. doi: 10.1084/jem.149.1.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Honjo T., Kataoka T. Organization of immunoglobulin heavy chain genes and allelic deletion model. Proc Natl Acad Sci U S A. 1978 May;75(5):2140–2144. doi: 10.1073/pnas.75.5.2140. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hurwitz J. L., Coleclough C., Cebra J. J. CH gene rearrangements in IgM-bearing B cells and in the normal splenic DNA component of hybridomas making different isotypes of antibody. Cell. 1980 Nov;22(2 Pt 2):349–359. doi: 10.1016/0092-8674(80)90345-1. [DOI] [PubMed] [Google Scholar]
- Hurwitz J. L., Tagart V. B., Schweitzer P. A., Cebra J. J. Patterns of isotype expression by B cell clones responding to thymus-dependent and thymus-independent antigens in vitro. Eur J Immunol. 1982 Apr;12(4):342–348. doi: 10.1002/eji.1830120416. [DOI] [PubMed] [Google Scholar]
- Jones P. P., Cebra J. J. Restriction of gene expression in B lymphocytes and their progeny. III. Endogenous IgA and IgM on the membranes of different plasma cell precursors. J Exp Med. 1974 Oct 1;140(4):966–976. doi: 10.1084/jem.140.4.966. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones P. P., Craig S. W., Cebra J. J., Herzenberg L. A. Restriction of gene expression in B lymphocytes and their progeny. II. Commitment to immunoglobulin heavy chain isotype. J Exp Med. 1974 Aug 1;140(2):452–469. doi: 10.1084/jem.140.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klaus G. G., Kunkl A. The role of germinal centres in the generation of immunological memory. Ciba Found Symp. 1981;84:265–280. doi: 10.1002/9780470720660.ch14. [DOI] [PubMed] [Google Scholar]
- Klinman N. R. Antibody with homogeneous antigen binding produced by splenic foci in organ culture. Immunochemistry. 1969 Sep;6(5):757–759. doi: 10.1016/0019-2791(67)90140-1. [DOI] [PubMed] [Google Scholar]
- Klinman N. R., Stone M. R. Role of variable region gene expression and environmental selection in determining the antiphosphorylcholine B cell repertoire. J Exp Med. 1983 Dec 1;158(6):1948–1961. doi: 10.1084/jem.158.6.1948. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lafrenz D., Teale J. M., Klinman N. R., Strober S. Surface IgG-bearing cells retain the capacity to secrete IgM. J Immunol. 1986 Mar 15;136(6):2076–2079. [PubMed] [Google Scholar]
- Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
- Maki R., Traunecker A., Sakano H., Roeder W., Tonegawa S. Exon shuffling generates an immunoglobulin heavy chain gene. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2138–2142. doi: 10.1073/pnas.77.4.2138. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marcu K. B., Schibler U., Perry R. P. Nuclear transcripts of mouse heavy chain immunoglobulin genes contain only the expressed class of C-region sequences. Science. 1979 Jun 8;204(4397):1087–1088. doi: 10.1126/science.109919. [DOI] [PubMed] [Google Scholar]
- Mather E. L., Nelson K. J., Haimovich J., Perry R. P. Mode of regulation of immunoglobulin mu- and delta-chain expression varies during B-lymphocyte maturation. Cell. 1984 Feb;36(2):329–338. doi: 10.1016/0092-8674(84)90226-5. [DOI] [PubMed] [Google Scholar]
- Nieuwenhuis P., Gastkemper N. A., Opstelten D. Histophysiology of follicular structures and germinal centres in relation to B cell differentiation. Ciba Found Symp. 1981;84:246–264. doi: 10.1002/9780470720660.ch13. [DOI] [PubMed] [Google Scholar]
- Obata M., Kataoka T., Nakai S., Yamagishi H., Takahashi N., Yamawaki-Kataoka Y., Nikaido T., Shimizu A., Honjo T. Structure of a rearranged gamma 1 chain gene and its implication to immunoglobulin class-switch mechanism. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2437–2441. doi: 10.1073/pnas.78.4.2437. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perlmutter A. P., Gilbert W. Antibodies of the secondary response can be expressed without switch recombination in normal mouse B cells. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7189–7193. doi: 10.1073/pnas.81.22.7189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rabbitts T. H., Forster A., Dunnick W., Bentley D. L. The role of gene deletion in the immunoglobulin heavy chain switch. Nature. 1980 Jan 24;283(5745):351–356. doi: 10.1038/283351a0. [DOI] [PubMed] [Google Scholar]
- Reichert R. A., Gallatin W. M., Weissman I. L., Butcher E. C. Germinal center B cells lack homing receptors necessary for normal lymphocyte recirculation. J Exp Med. 1983 Mar 1;157(3):813–827. doi: 10.1084/jem.157.3.813. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rose M. L., Birbeck M. S., Wallis V. J., Forrester J. A., Davies A. J. Peanut lectin binding properties of germinal centres of mouse lymphoid tissue. Nature. 1980 Mar 27;284(5754):364–366. doi: 10.1038/284364a0. [DOI] [PubMed] [Google Scholar]
- Rovera G., Ferrero D., Pagliardi G. L., Vartikar J., Pessano S., Bottero L., Abraham S., Lebman D. Induction of differentiation of human myeloid leukemias by phorbol diesters: phenotypic changes and mode of action. Ann N Y Acad Sci. 1982 Dec 10;397:211–220. doi: 10.1111/j.1749-6632.1982.tb43428.x. [DOI] [PubMed] [Google Scholar]
- Sakano H., Maki R., Kurosawa Y., Roeder W., Tonegawa S. Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes. Nature. 1980 Aug 14;286(5774):676–683. doi: 10.1038/286676a0. [DOI] [PubMed] [Google Scholar]
- Shimizu A., Takahashi N., Yaoita Y., Honjo T. Organization of the constant-region gene family of the mouse immunoglobulin heavy chain. Cell. 1982 Mar;28(3):499–506. doi: 10.1016/0092-8674(82)90204-5. [DOI] [PubMed] [Google Scholar]
- Stavnezer J., Abbott J., Sirlin S. Immunoglobulin heavy chain switching in cultured I.29 murine B lymphoma cells: commitment to an IgA or IgE switch. Curr Top Microbiol Immunol. 1984;113:109–116. doi: 10.1007/978-3-642-69860-6_21. [DOI] [PubMed] [Google Scholar]
- Symington F. W., Sprent J. A monoclonal antibody detecting an Ia specificity mapping in the I-A or I-E subregion. Immunogenetics. 1981;14(1-2):53–61. doi: 10.1007/BF00344299. [DOI] [PubMed] [Google Scholar]
- Teale J. M., Lafrenz D., Klinman N. R., Strober S. Immunoglobulin class commitment exhibited by B lymphocytes separated according to surface isotype. J Immunol. 1981 May;126(5):1952–1957. [PubMed] [Google Scholar]
- Teale J. M., Layton J. E., Nossal G. J. In vitro model for natural tolerance to self-antigens. Inhibition of the development of surface-immunoglobulin-negative lymphocytes into T-dependent responsive B cells by antigen. J Exp Med. 1979 Aug 1;150(2):205–217. doi: 10.1084/jem.150.2.205. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thorbecke G., Lerman S. P. Germinal centers and their role in immune responses. Adv Exp Med Biol. 1976;73(PT-A):83–100. doi: 10.1007/978-1-4684-3297-8_8. [DOI] [PubMed] [Google Scholar]
- Tilley S. A., Birshtein B. K. Unequal sister chromatid exchange. A mechanism affecting Ig gene arrangement and expression. J Exp Med. 1985 Aug 1;162(2):675–694. doi: 10.1084/jem.162.2.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
- White B. A., Bancroft F. C. Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. J Biol Chem. 1982 Aug 10;257(15):8569–8572. [PubMed] [Google Scholar]
- Yaoita Y., Honjo T. Deletion of immunoglobulin heavy chain genes from expressed allelic chromosome. Nature. 1980 Aug 28;286(5776):850–853. doi: 10.1038/286850a0. [DOI] [PubMed] [Google Scholar]
- Yefenof E., Sanders V. M., Snow E. C., Noelle R. J., Oliver K. G., Uhr J. W., Vitetta E. S. Preparation and analysis of antigen-specific memory B cells. J Immunol. 1985 Dec;135(6):3777–3784. [PubMed] [Google Scholar]
- Yelton D. E., Desaymard C., Scharff M. D. Use of monoclonal anti-mouse immunoglobulin to detect mouse antibodies. Hybridoma. 1981;1(1):5–11. doi: 10.1089/hyb.1.1981.1.5. [DOI] [PubMed] [Google Scholar]