Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. 1992 Sep 1; 176(3): 679–687.
PMCID: PMC2119370

In situ studies of the primary immune response to (4-hydroxy-3- nitrophenyl)acetyl. II. A common clonal origin for periarteriolar lymphoid sheath-associated foci and germinal centers


In the genetically restricted response that follows immunization with (4-hydroxy-3-nitrophenyl)acetyl coupled to protein carriers, two distinct populations of B cells are observed in the spleens of C57BL/6 mice. By 48 h postimmunization, foci of antigen-binding B cells appear along the periphery of the periarteriolar lymphoid sheaths. These foci expand to contain large numbers of antibody-forming cells that neither bind the lectin, peanut agglutinin, nor mutate the rearranged immunoglobulin variable region loci. Germinal centers containing peanut agglutinin-positive B cells can be observed by 96-120 h after immunization. Although specific for the immunizing hapten, these B cells do not produce substantial amounts of antibody, but are the population that undergoes somatic hypermutation and affinity-driven selection. Both focus and germinal center populations are pauciclonal, founded, on average, by three or fewer B lymphocytes. Despite the highly specialized roles of the focus (early antibody production) and germinal center (higher affinity memory cells) B cell populations, analysis of VH to D to JH joins in neighboring foci and germinal centers demonstrate that these B cell populations have a common clonal origin.

Full Text

The Full Text of this article is available as a PDF (1.7M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • THORBECKE GJ, KEUNING FJ. Antibody and gamma globulin formation in vitro in hemopoietic organs. J Infect Dis. 1956 Mar-Apr;98(2):157–171. [PubMed]
  • THORBECKE GJ, ASOFSKY RM, HOCHWALD GM, SISKIND GW. Gamma globulin and antibody formation in vitro. III. Induction of secondary response at different intervals after the primary; the role of secondary nodules in the preparation for the secondary response. J Exp Med. 1962 Sep 1;116:295–310. [PMC free article] [PubMed]
  • Tsiagbe VK, Linton PJ, Thorbecke GJ. The path of memory B-cell development. Immunol Rev. 1992 Apr;126:113–141. [PubMed]
  • MacLennan IC, Liu YJ, Oldfield S, Zhang J, Lane PJ. The evolution of B-cell clones. Curr Top Microbiol Immunol. 1990;159:37–63. [PubMed]
  • Nieuwenhuis P, Opstelten D. Functional anatomy of germinal centers. Am J Anat. 1984 Jul;170(3):421–435. [PubMed]
  • Jacob J, Kassir R, Kelsoe G. In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. I. The architecture and dynamics of responding cell populations. J Exp Med. 1991 May 1;173(5):1165–1175. [PMC free article] [PubMed]
  • Jacob J, Kelsoe G, Rajewsky K, Weiss U. Intraclonal generation of antibody mutants in germinal centres. Nature. 1991 Dec 5;354(6352):389–392. [PubMed]
  • Mäkelä O, Karjalainen K. Inherited immunoglobulin idiotypes of the mouse. Immunol Rev. 1977;34:119–138. [PubMed]
  • Jack RS, Imanishi-Kari T, Rajewsky K. Idiotypic analysis of the response of C57BL/6 mice to the (4-hydroxy-3-nitrophenyl)acetyl group. Eur J Immunol. 1977 Aug;7(8):559–565. [PubMed]
  • Reth M, Hämmerling GJ, Rajewsky K. Analysis of the repertoire of anti-NP antibodies in C57BL/6 mice by cell fusion. I. Characterization of antibody families in the primary and hyperimmune response. Eur J Immunol. 1978 Jun;8(6):393–400. [PubMed]
  • Bothwell AL, Paskind M, Reth M, Imanishi-Kari T, Rajewsky K, Baltimore D. Heavy chain variable region contribution to the NPb family of antibodies: somatic mutation evident in a gamma 2a variable region. Cell. 1981 Jun;24(3):625–637. [PubMed]
  • Grobler P, Buerki H, Cottier H, Hess MW, Stoner RD. Cellular bases for relative radioresistance of the antibody-forming system at advanced stages of the secondary response to tetanus toxoid in mice. J Immunol. 1974 Jun;112(6):2154–2165. [PubMed]
  • Liu YJ, Joshua DE, Williams GT, Smith CA, Gordon J, MacLennan IC. Mechanism of antigen-driven selection in germinal centres. Nature. 1989 Dec 21;342(6252):929–931. [PubMed]
  • Berek C, Berger A, Apel M. Maturation of the immune response in germinal centers. Cell. 1991 Dec 20;67(6):1121–1129. [PubMed]
  • Coico RF, Bhogal BS, Thorbecke GJ. 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]
  • Linton PJ L, Decker DJ, Klinman NR. Primary antibody-forming cells and secondary B cells are generated from separate precursor cell subpopulations. Cell. 1989 Dec 22;59(6):1049–1059. [PubMed]
  • Clarke SH, Huppi K, Ruezinsky D, Staudt L, Gerhard W, Weigert M. Inter- and intraclonal diversity in the antibody response to influenza hemagglutinin. J Exp Med. 1985 Apr 1;161(4):687–704. [PMC free article] [PubMed]
  • Allen D, Cumano A, Dildrop R, Kocks C, Rajewsky K, Rajewsky N, Roes J, Sablitzky F, Siekevitz M. Timing, genetic requirements and functional consequences of somatic hypermutation during B-cell development. Immunol Rev. 1987 Apr;96:5–22. [PubMed]
  • Desiderio SV, Yancopoulos GD, Paskind M, Thomas E, Boss MA, Landau N, Alt FW, Baltimore D. Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells. Nature. 1984 Oct 25;311(5988):752–755. [PubMed]
  • Max EE, Seidman JG, Leder P. Sequences of five potential recombination sites encoded close to an immunoglobulin kappa constant region gene. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3450–3454. [PMC free article] [PubMed]
  • Shlomchik M, Mascelli M, Shan H, Radic MZ, Pisetsky D, Marshak-Rothstein A, Weigert M. Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J Exp Med. 1990 Jan 1;171(1):265–292. [PMC free article] [PubMed]
  • Weiss U, Rajewsky K. The repertoire of somatic antibody mutants accumulating in the memory compartment after primary immunization is restricted through affinity maturation and mirrors that expressed in the secondary response. J Exp Med. 1990 Dec 1;172(6):1681–1689. [PMC free article] [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • Tindall KR, Kunkel TA. Fidelity of DNA synthesis by the Thermus aquaticus DNA polymerase. Biochemistry. 1988 Aug 9;27(16):6008–6013. [PubMed]
  • Liu YJ, Zhang J, Lane PJ, Chan EY, MacLennan IC. Sites of specific B cell activation in primary and secondary responses to T cell-dependent and T cell-independent antigens. Eur J Immunol. 1991 Dec;21(12):2951–2962. [PubMed]
  • Gu H, Tarlinton D, Müller W, Rajewsky K, Förster I. Most peripheral B cells in mice are ligand selected. J Exp Med. 1991 Jun 1;173(6):1357–1371. [PMC free article] [PubMed]
  • Cumano A, Rajewsky K. Clonal recruitment and somatic mutation in the generation of immunological memory to the hapten NP. EMBO J. 1986 Oct;5(10):2459–2468. [PMC free article] [PubMed]
  • Tao W, Bothwell AL. Development of B cell lineages during a primary anti-hapten immune response. J Immunol. 1990 Nov 15;145(10):3216–3222. [PubMed]
  • Blier PR, Bothwell AL. The immune response to the hapten NP in C57BL/6 mice: insights into the structure of the B-cell repertoire. Immunol Rev. 1988 Oct;105:27–43. [PubMed]
  • Blier PR, Bothwell A. A limited number of B cell lineages generates the heterogeneity of a secondary immune response. J Immunol. 1987 Dec 15;139(12):3996–4006. [PubMed]
  • Weiss U, Zoebelein R, Rajewsky K. Accumulation of somatic mutants in the B cell compartment after primary immunization with a T cell-dependent antigen. Eur J Immunol. 1992 Feb;22(2):511–517. [PubMed]
  • McHeyzer-Williams MG, Nossal GJ, Lalor PA. Molecular characterization of single memory B cells. Nature. 1991 Apr 11;350(6318):502–505. [PubMed]
  • Kroese FG, Wubbena AS, Seijen HG, Nieuwenhuis P. The de novo generation of germinal centers is an oligoclonal process. Adv Exp Med Biol. 1988;237:245–250. [PubMed]
  • Linton PJ, Lo D, Lai L, Thorbecke GJ, Klinman NR. Among naive precursor cell subpopulations only progenitors of memory B cells originate germinal centers. Eur J Immunol. 1992 May;22(5):1293–1297. [PubMed]
  • Golding GB, Gearhart PJ, Glickman BW. Patterns of somatic mutations in immunoglobulin variable genes. Genetics. 1987 Jan;115(1):169–176. [PMC free article] [PubMed]
  • Foote J, Milstein C. Kinetic maturation of an immune response. Nature. 1991 Aug 8;352(6335):530–532. [PubMed]
  • Kupp LI, Kosco MH, Schenkein HA, Tew JG. Chemotaxis of germinal center B cells in response to C5a. Eur J Immunol. 1991 Nov;21(11):2697–2701. [PubMed]
  • Zwirner J, Felber E, Schmidt P, Riethmüller G, Feucht HE. Complement activation in human lymphoid germinal centres. Immunology. 1989 Feb;66(2):270–277. [PMC free article] [PubMed]
  • Crispe IN, Bevan MJ. Expression and functional significance of the J11d marker on mouse thymocytes. J Immunol. 1987 Apr 1;138(7):2013–2018. [PubMed]
  • Liu Y, Jones B, Aruffo A, Sullivan KM, Linsley PS, Janeway CA., Jr Heat-stable antigen is a costimulatory molecule for CD4 T cell growth. J Exp Med. 1992 Feb 1;175(2):437–445. [PMC free article] [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    NCBI Bookshelf books that cite the current articles.
  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • MedGen
    Related information in MedGen
  • Nucleotide
    Primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
  • Protein
    Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...