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L S Wicker

Publications and source records attributed to L S Wicker.

64 records · Page 4Linked to original sources
PubMed1985

Regulation of T15 idiotype dominance. II. Genes unlinked to the Igh locus regulate T15 dominance of the secondary adoptive transfer response to phosphocholine.

We have studied the idiotype and fine specificity of the secondary immune response to phosphocholine (PC) in C57BL (B10, B10.D2, and B.C8) and BALB (BALB/c, BAB-14, and C.B20) congenic strains of mice. In vivo IgM responses of mice from these two genetic backgrounds differed in their T15 idiotypic representation. BALB strains expressed the T15 idiotype on greater than 90% of their IgM, PC-specific plaque-forming cells (PFC), whereas C57BL strains expressed the T15 idiotype on approximately 50% of their IgM PFC. All strains examined expressed greater than 75% PC-inhibitable, VHPC idiotype-positive, IgM PFC. The IgG3 and IgA memory responses were similar to the IgM memory response; BALB strains produced a higher proportion of T15+ PFC than C57BL strains; however, the majority of IgG3 and IgA PFC in all strains were VHPC+, and PC-inhibitable. In contrast, the IgG1 memory response was not dominated by T15+, VHPC+, PC-inhibitable PFC in any of the strains tested. The IgG1 PFC required nitrophenylphosphocholine (NPPC) for efficient inhibition. The IgG2 memory response generally mimicked the IgG1 response with respect to idiotype and specificity. These data demonstrate that the representation of the T15 idiotype in the anti-PC immune response is determined by genes outside both the MHC and Igh genetic loci. Control of T15 expression in secondary IgM, IgG3, and IgA anti-PC responses was examined by using a cell-mixing protocol with primed T and B cells from BALB/c and B10.D2 mice. T15 representation in these responses was determined by the genotype of the B cell, not by the genotype of the helper T cell. Similarly, the B cell genotype was responsible for the idiotypic profile of a primary, in vitro, T-dependent, anti-PC response.

Alleles↗
PubMed1984

Immunodominant protein epitopes. I. Induction of suppression to hen egg white lysozyme is obliterated by removal of the first three N-terminal amino acids.

The lack of response to hen egg white lysozyme (HEL) by C57BL (H-2b) mice has been demonstrated previously to be related to the induction of suppressor T (Ts) cells which recognize the amino terminal region of HEL. In this report, the nature of the protein determinant required for Ts cell induction is more precisely detailed using des-1,2,3-HEL (AP-HEL) prepared with an aminopeptidase purified from Aeromonas proteolytica . Remarkably, the removal of just these three amino acids obliterates the ability of HEL to induce Ts cells specific for HEL. Additionally, in contrast to HEL, AP-HEL is able to prime for an in vitro T cell proliferative response to either AP-HEL or HEL. Thus, removal of a very limited region of a protein antigen can drastically alter its immunogenic properties.

Animals↗
PubMed1984

Immunodominant protein epitopes. II. The primary antibody response to hen egg white lysozyme requires and focuses upon a unique N-terminal epitope.

The antibody response to a defined protein antigen, hen egg white lysozyme (HEL) has been investigated using an aminopeptidase-treated HEL molecule, des-1,2,3-HEL (AP-HEL). Surprisingly, removal of these three N-terminal residues eliminates an epitope which is a dominant B cell determinant recognized in the primary antibody response to HEL. Thus, the initial antibody response focuses on a very small region of the molecule. Even more striking is the observation that removal of this epitope markedly reduces the immunogenicity of HEL. Therefore, the epitope is not only the focus of the primary antibody response, but is essential for the initiation of the response. This report demonstrates that a selective mechanism must be activated during the response to this protein antigen. Of the multitude of B cell determinants present on HEL, only a limited number are focused upon by the immune system.

Amino Acid Sequence↗
PubMed1984

H-2 hierarchy in the IR-gene controlled responses to hapten-modified mouse serum albumin.

Five hapten-modified autogenous mouse serum albumins (MSA), TNP11MSA, FITC8MSA, DNP64MSA, DNP5MSA, and PC2MSA, were tested for their ability to induce hapten-specific antibody responses in H-2 congenic mice of the H2d, H-2b, H-2a, and H-2f haplotypes. Four of the five modified MSAs, TNP11MSA, FITC8MSA, DNP64MSA, and PC2MSA, stimulated responses found to be under H-2-linked Ir gene control, whereas DNP5MSA failed to induce responses in any strain tested. H-2d, H-2D, and H-2a mice responded to FITC8MSA; H-2d and H-2b responded to TNP11MSA; and only H-2d mice were high responders to DNP64MSA and PC2MSA. H-2f mice failed to respond to any of the stimulating antigens. Thus, a hierarchy of H-2 haplotypes was observed in the responsiveness to modified MSA with H-2d greater than H-2b greater than H-2a greater than H-2f. Primed lymph node cells from PC2MSA immunized H-2d mice were challenged with antigen in vitro to assess the nature of the determinant recognized by T cells in the response to modified MSA. Lymph node cells proliferated only when challenged with PC2MSA. Unmodified MSA or TNP11MSA did not stimulate a proliferative response, suggesting that the immune T cells recognize a neodeterminant present on the modified PC2MSA.

Animals↗
PubMed1983

The asymmetry in idiotype-isotype expression in the response to phosphocholine is due to divergence in the expressed repertoires of Lyb-5+ and Lyb-5- B cells.

The X-linked CBA/N immune defect was used to investigate the roles of Lyb-5- and Lyb-5+ B cells in the memory response to PC-KLH (phosphocholine-conjugated keyhole limpet hemocyanin). (CBA/N X BALB/c)F1 (CB) male mice express the xid mutation and thereby lack the Lyb-5+ B cell subset, whereas their female littermates are normal and express both Lyb-5+ and Lyb-5- B cells. After priming with PC-conjugated hemocyanin (PC-Hy) in complete Freund's adjuvant, female B cells produce three phenotypic sets of PC-KLH-specific antibody. The first set (group I) is dominated by T15+, IgM, IgA, and IgG3, PC-specific antibodies. The second subset (group II) is specific for phenylphosphocholine (PPC), and is dominated by T15-, IgG1, and IgG2 antibodies. The third set (group III) recognizes an epitope(s) composed of both the PPC hapten and carrier determinants. PC-Hy-primed B cells from immune defective CB male mice produce the same number of IgG1 and IgG2 plaque-forming cells (PFC) as do PC-Hy-primed normal female cells, and these PFC are also predominantly T15- and PPC specific (group II). In addition, a significant amount of group III IgG1 and IgG2 antibody is observed in the immune defective male response. In contrast to female B cells, immune defective male B cells produce a low IgM, IgA, and IgG3 memory response that is not composed of PC-specific (group I) antibodies; in fact, most of these antibodies arise from group III precursors and are not inhibited by either PC or PPC. PC-specific antibodies usually represent less than 25% of the anti-PC-KLH response in immune defective mice; however, these PC-specific antibodies are predominantly T15-. These data suggest that the Lyb-5-B cells in both normal and immune defective mice produce the T15-, IgG1, and IgG2 antibodies that dominate the secondary immune response to PC-KLH, and that the Lyb-5+ B cells produce the T15+, IgM, IgA, and IgG3 portion of the secondary response in normal mice. This hypothesis was confirmed by priming normal mice with the R36a strain of Streptococcus pneumoniae or with PC-Hy in saline. These forms of PC-antigen prime only the Lyb-5+ B cell subset. The adoptive transfer of these two B cell sources results in an anti-PC-KLH response that is T15 dominant and totally PC inhibitable.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1982

Antibodies from the Lyb-5- B cell subset predominate in the secondary IgG response to phosphocholine.

The X-linked CBA/N immune defect was used to investigate the role of the Lyb-5- B cell subset in phosphocholine- (PC) specific memory responses. Immune-defective mice, which express only the Lyb-5- B cell subset, are unable to mount a primary or secondary T15+, IgM response to PC but can produce a substantial secondary IgG response. The majority of these IgG anti-PC antibodies are T15- and can be inhibited by phenylphosphocholine, but not PC. Normal mice, which possess Lyb-5+ and Lyb-5- B cells, produce both IgM and IgG anti-PC antibodies; however, there is a striking difference in the idiotype and fine specificity of antibodies expressed by these two classes. The IgM anti-PC antibodies are T15+ and PC-inhibitable, whereas the IgG antibodies are identical to those observed in the immune-defective mice, i.e., T15- and PC-noninhibitable. This unexpected difference in both idiotype and fine specificity between IgM and IgG anti-PC antibodies results from activation of different B cell subsets. Lyb-5+ B cells produce T15+, PC-inhibitable IgM antibodies, whereas T15-, PC-noninhibitable IgG antibodies are produced by Lyb-5- B cells. These data indicate that a majority of the thymus-dependent, anti-PC IgG memory responses arises from Lyb-5- B cells.

Animals↗
PubMed1982

Regulation of T15 idiotype dominance. I. Mice expressing the xid immune defect provide normal help to T15+ B cell precursors.

The immune response to phosphocholine (PC) in many strains of mice is dominated by the T15 idiotype family of anti-PC antibodies. By introducing the CBA/N X-linked immune defect (xid gene) into these mice, one profoundly alters their ability to make a T15-predominant, IgM anti-PC response. This loss of T15 dominance in mice expressing the xid gene is not due to the presence of suppressor T cells or the lack of T15 idiotype-specific helper cells in these mice. Thus, one can reconstitute a T15 idiotype-dominant response in immune defective mice with B cells from normal mice, and in adoptive transfer assays the primed T helper cells from immune-defective mice provide qualitatively the same help to normal B cells as the T helper cells from normal mice. T15 idiotype dominance appears to be controlled by the expression and activation of Lyb-5+ PC-specific B cells. Thus, the majority of T15+ B cell precursors are restricted to this B cell subset, whereas the Lyb-5- B cell subset contains predominantly T15-, anti-PC B cell precursors, which produce mainly IgG antibodies after activation by PC-containing antigens.

Animals↗
PubMed1981

Two distinct high immune response phenotypes are both controlled by H-2 genes mapping K or I-A.

Murine responses to immunization with 2, 4, 6-trinitrophenyl (TNP) conjugated to autogenous mouse serum albumin (MSA) in complete Freund's adjuvant (CFA) are controlled by a gene(s) in the K or I-A region of H-2 complex. High immune responses of both H-2d and H-2b mice have been mapped to this region of the major histocompatibility complex. No modifying effects were observed from genes to the right of I-A in either responder haplotype. High responsiveness controlled by Kb or I-Ab is inherited with complete or partial recessivity, depending on the route of immunization and the sex of the responder. However, high responsiveness controlled by Kd or I-Ad is inherited dominantly. This unusual pattern of inheritance of immune responsiveness to TNP-MSA is consistent with the genetic mapping to K or I-A. TNP-MSA-specific T-cell reactivity following immunization with TNP-MSA in vivo was examined utilizing a T-cell-dependent proliferation assay in vitro with cells obtained from high or low responder mice. Genetic mapping and mode of inheritance in this assay for antigen-specific T-cell reactivity corresponded with results obtained from a plaque-forming cell (PFC) assay measuring antibody production by B cells. Both the proliferative and PFC responses are probably under the same Ir gene control. Both gene dosage effects and Ir-gene-product interaction could influence the generation of specific immune responsiveness in F1 hybrids between high and low responders to TNP-MSA.

Animals↗
PubMed1980

Genetic control of susceptibility to Cryptococcus neoformans in mice.

Inbred mice injected intravenously with 5 x 10(6) cells of Cryptococcus neoformans showed two patterns of survival: sensitive (A/WySn, A.BY, A/J, DBA/2J, NZB/B1NJ, and SWR/J) and resistant [C57BL/10Sn, B10.A, B10.A (2R), B10.S (7R),C57BR/cdJ, C58/J, C3H/HeJ, BALB/c, DBA/1J, and SJL/J]. Relative susceptibility based on survival time was shown to correspond to differences obtained for 50% lethal dose values. Either decreasing the dose of organisms or changing to the intraperitoneal route of inoculation resulted in prolonged survival times, but neither change affected the observed patterns of survival. F1 hybrids between different sensitive strains were also sensitive, whereas F1 hybrids between sensitive and resistant strains were resistant, indicating a dominant mode of inheritance. Sensitivity and resistance were shown to be under single gene control by segregation analysis in F2 progeny produced by inbreeding (B10.A x A/WySn)F1 hybrids and in (F1 x A/WySn) backcross progeny. Blood obtained from parental strains, F1, F2, and backcross hybrids was tested for the presence or absence of hemolytic complement. Mice lacking hemolytic complement activity in their sera are homozygous for the Hc(0) allele at the Hc locus on chromosome 2 and are deficient in the complement component C5. A 1:1 correspondence was found between C5 deficiency and sensitivity to C. neoformans. Resistance was shown to cosegregate with the presence of hemolytic complement in the F2 and the backcross progenies.

Animals↗