scholarly journals CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE

1968 ◽  
Vol 128 (3) ◽  
pp. 437-457 ◽  
Author(s):  
G. M. Shearer ◽  
G. Cudkowicz ◽  
Mary St. James Connell ◽  
R. L. Priore
Keyword(s):  
Cellular Differentiation ◽  
Sheep Erythrocyte ◽  
Donor Cell ◽  
Cell Suspensions ◽  
Antibody Responses ◽  
Primary Immune Response ◽  
Cell Populations ◽  
Spleen Cells ◽  
Experimental Conditions ◽  
Antibody Class

Spleen cell suspensions of unprimed donor mice containing precursors of immunocytes have been transplanted into X-irradiated recipient mice. In the presence of antigen (sheep erythrocytes) these precursors, called antigen-sensitive units, gave rise to progeny cells secreting specific antibody. We studied quantitatively the production of cells releasing IgM hemolysins (direct plaque-forming cells), IgG hemolysins (indirect plaque-forming cells), and hemagglutinins (cluster-forming cells). We found that each of these immunocyte populations was distinct, i.e., that cells releasing agglutinins did not, as a rule, release hemolysins, and vice versa. We also found that cell populations secreting IgM hemolysins did not shift, under certain experimental conditions, to the production of IgG hemolysins during the primary immune response. By transplanting graded numbers of spleen cells, we succeeded in limiting to one or a few the number of antigen-sensitive units that reached the recipient spleen. We estimated thereby the frequency of antigen-sensitive units in donor cell suspensions and tested their potential for production of immunocytes of more than one type. Our results indicated that antigen-sensitive units were unipotent for they displayed in the spleens of unprimed donors the same restrictions of function and heterogeneity (antibody-specificity differentiation, antibody-class differentiation) found among antibody-forming cells. Furthermore, antigen-sensitive precursors for direct plaque-forming cells, indirect plaque-forming cells, and cluster-forming cells were detected in the spleens of unprimed mice in different frequencies, i.e., 1 in ∼ 106, 1 in ∼ 7 x 106, and 1 in ∼ 19 x 106 spleen cells, respectively. We concluded that relatively advanced differentiation of potentially competent cells occurs before sheep erythrocyte administration. The relevance of this finding for the broad spectrum of immunologic reactivities and for the heterogeneity of antibody responses to given antigens was discussed.

scholarly journals CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE

1969 ◽  
Vol 129 (1) ◽  
pp. 185-199 ◽  
Author(s):  
G. M. Shearer ◽  
G. Cudkowicz ◽  
R. L. Priore
Keyword(s):  
Immune System ◽  
Specific Antibody ◽  
Cellular Differentiation ◽  
Single Cells ◽  
Donor Cell ◽  
Cell Suspensions ◽  
The Other ◽  
Spleen Cells ◽  
Igg Antibody ◽  
Differentiated Cells

Spleen cell suspensions of primed donor mice containing precursors of immunocytes have been transplanted into X-irradiated recipient mice 122–138 days after immunization. Following secondary stimulation with antigen (sheep erythrocytes), these precursors, called antigen-sensitive units (ASU), gave rise to progeny cells secreting specific antibody in the spleens of recipients. Single cells releasing IgM hemolysins (direct plaque-forming cells or PFC), IgG hemolysins (indirect PFC), and hemagglutinins (cluster-forming cells or CFC) were enumerated. By transplanting graded and limiting numbers of primed spleen cells, inocula were found which contained one or a few ASU reaching the recipient spleens. We estimated, thereby, the frequency of ASU detectable by our procedures in donor cell suspensions. The values obtained from direct and in-indirect plaque assays, and from cluster assays were 1 in ∼8.0 x 105, 1 in ∼4.4 x 105, and 1 in ∼5.9 x 105 nucleated spleen cells, respectively. The number of splenic ASU for direct PFC was not greater than that of unimmunized mice; however, immunization greatly increased the number of splenic ASU for indirect PFC and for CFC. By applying to each recipient spleen direct and indirect plaque tests and cluster tests, we found that positivity for each type of immunocyte was independent from that of the other two types. These results confirm the unipotent nature of splenic ASU in general, and document the commitment of ASU primed with SRBC to generate progeny cells secreting antibody of a single molecular (IgM or IgG) or functional (lysin or agglutinin) class. We concluded that splenic ASU are composed of relatively differentiated cells of the immune system of mice. With respect to specificity and class differentiation, ASU appear to be as specialized as antibody-producing cells themselves. Our results did not support the view that ASU-derived clonal populations shift from IgM to IgG antibody production.

scholarly journals REGULATION OF ANTIBODY RESPONSE BY CELLS EXPRESSING HISTAMINE RECEPTORS

1972 ◽  
Vol 136 (5) ◽  
pp. 1302-1307 ◽  
Author(s):  
G. M. Shearer ◽  
Kenneth L. Melmon ◽  
Yacob Weinstein ◽  
Michael Sela
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Serum Albumin ◽  
Sheep Erythrocyte ◽  
Antibody Responses ◽  
Rabbit Serum ◽  
Spleen Cells ◽  
Surface Receptors ◽  
Cell Responses ◽  
A Cell

Spleen cells from immunized and unimmunized mice were either passed over histamine-rabbit serum albumin-Sepharose columns or rabbit serum albumin-Sepharose control columns. The immune response potential of 5 x 106 cells excluded from the two columns were compared with each other, and with an equal number of unfiltered cells by injection of the cell suspensions mixed with sheep erythrocytes into irradiated, syngeneic recipients. The direct and indirect anti-sheep erythrocyte plaque-forming cell responses generated by the cells passed over the histamine-bead column were significantly greater than the responses resulting from the inocula of unfiltered cells or cells passed over control columns. These results indicate the existence of a cell population expressing surface receptors for histamine, which functions to regulate antibody responses.

scholarly journals CELL INTERACTIONS IN THE IMMUNE RESPONSE IN VITRO

1972 ◽  
Vol 135 (5) ◽  
pp. 1049-1058 ◽  
Author(s):  
Marc Feldmann
Keyword(s):  
Thoracic Duct ◽  
Glass Bead ◽  
Gamma Globulin ◽  
Antibody Responses ◽  
Cell Populations ◽  
Spleen Cells ◽  
Cooperative Response ◽  
Exact Function ◽  
Immune Response In Vitro

The requirement for macrophages in thymus-dependent antibody responses was studied in vitro. Three different macrophage-deficient cell populations were studied: spleen cells passed through a glass bead column at 37°C, spleen cells cultured with specific antimacrophage serum, and thoracic duct lymphocytes. These cell populations from mice primed to dinitrophenylated (DNP) fowl gamma globulin were unable to respond to the homologous conjugate in vitro. DNP-reactive B cells were present in normal proportions, since all three macrophage-depleted populations responded normally to macrophage-independent and thymus-independent DNP flagella. Carrier-reactive T cells were present, as the helper capacity of carrier-primed spleen cells was the same as carrier-primed lymphocytes, and thoracic duct lymphocytes are a well-established source of helper cells. The inhibition of the cooperative response was thus due to removal of macrophages, and this was proven by restoration of thymus-dependent anti-DNP responses by small numbers of anti-θ-treated peritoneal exudate cells. These results suggest that macrophages are essential in cell collaboration, While their exact function in cell collaboration is not yet known, the above observation suggests that the mechanism of T-B collaboration involves the surface of macrophages.

scholarly journals ANTIBODY RESPONSES TO ANTIGENIC DETERMINANTS OF INFLUENZA VIRUS HEMAGGLUTININ

1974 ◽  
Vol 140 (6) ◽  
pp. 1571-1578 ◽  
Author(s):  
Jean-Louis Virelizier ◽  
Anthony C. Allison ◽  
Geoffrey C. Schild
Keyword(s):  
Influenza Virus ◽  
Antibody Responses ◽  
Secondary Response ◽  
Antigenic Determinants ◽  
Memory Cells ◽  
Spleen Cells ◽  
Experimental Conditions ◽  
Influenza Virus Hemagglutinin ◽  
Kinetics Of ◽  
Antibody Secretion

Mice immunized sequentially with two related influenza virus hemagglutinins (HA) produced a secondary antibody response with two different specificities. Some antibodies were specific for determinants common to both HA's. Paradoxically, some antibodies were directed to determinants existing only in the HA first encountered. Primed spleen cells treated with anti-θ serum and complement were transferred from animals immunized with the first HA to either normal, irradiated, or thymus-deprived recipients. These memory cells were boosted in the recipients with either the homologous or the heterologous cross-reacting HA. B-memory lymphocytes were shown to be directly triggered by both HA's and to be able to secrete, independently of T lymphocytes, antibodies to both kinds of determinants. However, T cells were shown to modulate this secondary response by either enhancing or suppressing antibody secretion by B-memory cells, depending on experimental conditions. These results are discussed in terms of antigen recognition by B cells and of kinetics of development of immunological memory.

scholarly journals EFFECT OF RECENT ANTIGEN PRIMING ON ADOPTIVE IMMUNE RESPONSES

1973 ◽  
Vol 138 (1) ◽  
pp. 143-162 ◽  
Author(s):  
J. Sprent ◽  
J. F. A. P. Miller
Keyword(s):  
Immune Responses ◽  
B Lymphocytes ◽  
Transient State ◽  
Antibody Responses ◽  
Partial Recovery ◽  
Cell Transfer ◽  
Spleen Cells ◽  
Experimental Conditions ◽  
Mesenteric Lymph ◽  
Normal Spleen

When spleen, mesenteric lymph node, or Peyer's patch cells from mice primed 24 h before with either sheep erythrocytes (SRC) or horse erythrocytes (HRC) were transferred together with both SRC and HRC to irradiated mice, antibody responses measured 7 days later were very low to the priming antigen but high to the other antigen. This was demonstrated either by measuring numbers of antibody-forming cells in spleen or levels of hemagglutinins in serum. Specific unresponsiveness of the transferred cells was evident in both the 19S and 7S responses. It was observed only when strict experimental conditions were followed: (a) the cell donors had to be primed with not less than 109 erythrocytes given intravenously; (b) the cells had to be transferred between 1 and 2 days after antigen priming; (c) antibody responses in the recipients were measured within 7 days of cell transfer, i.e., partial recovery was evident by 11 days; (d) the transferred cells had to be challenged in the recipients within 1 day after cell transfer: when challenge was delayed for 5 days or longer, responsiveness returned. The failure of cells from recently primed donors to respond to the priming antigen on adoptive transfer could be overcome by supplementing with normal spleen cells, but not with thymus alone or bone marrow alone. This implied that unresponsiveness occurred at the levels of both T and B lymphocytes, and was not due to a suppressive influence exerted by T cells. Further work is in progress to determine the mechanism of this transient state of specific unresponsiveness.

scholarly journals Immunosuppression of anti-sheep erythrocyte responses by glycerol teichoic acid immune complexes

1980 ◽  
Vol 30 (3) ◽  
pp. 723-727
Author(s):  
R W Bolton
Keyword(s):  
Sheep Erythrocyte ◽  
Serum Antibody ◽  
Teichoic Acid ◽  
Antibody Responses ◽  
Sprague Dawley ◽  
Experimental Conditions ◽  
Naturally Occurring ◽  
Sprague Dawley Rats ◽  
Naturally Occurring Antibodies ◽  
Antigenic Competition

Sprague-Dawley rats which produce "naturally occurring" antibodies to glycerol teichoic acid (GTA) displayed immunosuppression of anti-sheep erythrocyte plaque-forming cell and serum antibody responses when a single dose of lipid-free GTA was administered 24 h before immunization. Such suppression was enhanced by administering GTA complexed with anti-GTA immunoglobulin G. Animals fed a GTA-free diet produced no anti-GTA immunoglobulins and failed to show GTA-mediated immunosuppression under similar experimental conditions. However, when those animals were given GTA-anti-GTA complexes, suppression was evident. The results suggested antigenic competition mediated by immune complex-activated suppressor T cells. Lipid-free GTA did not stimulate serum antibody responses under the experimental conditions employed.

scholarly journals HAPTEN-SPECIFIC IgE ANTIBODY RESPONSES IN MICE

1973 ◽  
Vol 138 (3) ◽  
pp. 538-556 ◽  
Author(s):  
Toshiyuki Hamaoka ◽  
David H. Katz ◽  
Baruj Benacerraf
Keyword(s):  
T Lymphocytes ◽  
Antibody Production ◽  
Adoptive Transfer ◽  
B Lymphocyte ◽  
Antibody Responses ◽  
Spleen Cells ◽  
Igg Antibody ◽  
Ige Antibody ◽  
Antibody Class

The present studies have established conditions for the demonstration of cooperative interactions between specific T and B lymphocyte populations in the development of IgE antibody responses in vivo in mice. This has been accomplished by utilizing a system which permits the successful adoptive transfer to irradiated recipients of DNP-specific secondary IgE responses with spleen cells from suitably primed syngeneic donor mice. Thus, adoptively transferred DNP-KLH or DNP-ASC-primed spleen cells produced high levels of anti-DNP antibodies of both IgE and IgG antibody classes in response to challenge with the appropriate homologous priming conjugate but failed to develop more than meager responses to the reciprocal heterologous conjugate. However, when spleen cells from donors primed to the second carrier were concomitantly transferred with hapten-primed lymphocytes, secondary IgE ant-DNP responses were consistently obtained upon challenge with the heterologous conjugate. Moreover, we have been able to elicit augmented primary IgE anti-DNP antibody responses to either DNP-ASC or DNP-KLH after adoptive transfer of spleen cells from donors primed only to the carrier, ASC or KLH, respectively. This adoptive transfer system has enabled us to provide direct proof for the participation of θ-bearing T lymphocytes in antibody responses of the IgE class. Thus, the capacity of ASC-primed spleen cells to effectively cooperate with the DNP-KLH-primed lymphocytes in the adoptive secondary response to DNP-ASC could be abolished by in vitro treatment of such cells with anti-θ serum plus complement. This was true not only for the anti-DNP response of the IgG antibody class, but for the IgE antibody class as well. These studies have, furthermore, demonstrated the capacity to stimulate secondary anti-DNP antibody production in vivo by the concomitant administration of the DNP and relevant carrier determinants on separate molecules. This was more readily seen in the IgE than in the IgG antibody class. Thus, DNP-ASC-primed cells developed significant IgE, but more variable IgG, anti-DNP responses upon challenge with DNP-KLH plus unconjugated ASC. Antibody responses of both classes elicited in this manner were appreciably improved by the transfer of additional carrier (ASC)-primed cells. These and other results presented herein suggest that IgE B lymphocyte precursors may be inherently more sensitive than IgG B cells to at least certain of the functions of T lymphocytes concerned with regulatory mechanisms involved in antibody production.

scholarly journals SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE

1970 ◽  
Vol 131 (2) ◽  
pp. 223-234 ◽  
Author(s):  
Harvey Cantor ◽  
Richard Asofsky ◽  
Norman Talal
Keyword(s):  
Host Response ◽  
Lymphoid Cells ◽  
Cell Populations ◽  
Spleen Cells ◽  
Graft Versus Host ◽  
Minimum Number ◽  
Number Of Cells

The ability of spleen cells from young (3 month) and old (1 yr) NZB mice to induce GVH reactions in newborn C57BL/6N mice was compared quantitatively using the Simonsen spleen assay. Young NZB cells were five times more reactive than cells from older mice. The minimum number of cells producing detectable reactions was 2 x 106 for the young and 10 x 106 for the old. Young and old cells combined and injected together produced GVH reactions quantitatively similar to those obtained with inocula composed of young cells alone. Mixtures of two cell populations producing no detectable reactions when injected separately into different recipients (1 x 106 young cells and 4 x 106 old cells) produced reactions approximately equal to those obtained with 5 x 106 young cells. As few as 0.25 x 106 young cells were sufficient to effect a reaction when combined with 4.75 x 106 old unreactive cells. Viability of both cell populations was essential for GVH reactivity. This evidence of synergy in GVH reactions indicates that old NZB spleen cells can be rendered immunologically more reactive in the presence of a normally reactive population.

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