scholarly journals INITIATION OF ANTIBODY RESPONSES BY DIFFERENT CLASSES OF LYMPHOCYTES

1972 ◽  
Vol 136 (4) ◽  
pp. 851-871 ◽  
Author(s):  
Samuel Strober
Keyword(s):  
B Cells ◽  
Antibody Response ◽  
Thoracic Duct ◽  
Primary Response ◽  
Thoracic Duct Lymph ◽  
Secondary Antibody ◽  
Duct Cells ◽  
Precursor B Cells ◽  
B1 Cells ◽  
Horse Spleen Ferritin

The life-span and migratory characteristics of rat thoracic duct cells which initiate the adoptive primary and secondary antibody response to diphtheria toxoid (DT) and horse spleen ferritin (HSF) were investigated. The experimental results show that thoracic duct lymphocytes from normal (unimmunized) donors are able to restore the adoptive response of irradiated hosts to HSF. Thoracic duct cells passaged through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) showed a marked reduction in their restorative action as compared with unpassaged cells. In addition, the restorative action of cells from donors treated with thymidine-3H for 48 hr before cannulation of the thoracic duct was markedly decreased. This indicates that a population of lymphocytes involved in the adoptive primary response is unable to recirculate from the blood to the lymph and is turning over rapidly (short lived). The nonrecirculating, short-lived lymphocytes are proably "B" cells, since a combination of spleen cells from neonatally thymectomized rats and passaged or thymidine-3H-treated cells restores a vigorous response to HSF. On the other hand, passaged or thymidine-3H-treated thoracic duct cells from donors immunized to DT or HSF are able to restore a vigorous adoptive secondary antibody response. Experiments with the hapten-protein conjugate, DNP-DT, show that the majority of both helper ("T") and precursor ("B") cells are able to recirculate and are slowly turning over (long lived). The findings suggest that T lymphocytes involved in both the primary and secondary antibody response are recirculating, long-lived cells. However, B lymphocytes involved in the primary response are nonrecirculating, short-lived cells ("B1" cells) which undergo a fundamental physiological change to recirculating, long-lived cells ("B2" cells) involved in the secondary antibody response.

scholarly journals CELL-TO-CELL INTERACTION IN THE IMMUNE RESPONSE

1971 ◽  
Vol 134 (1) ◽  
pp. 66-82 ◽  
Author(s):  
J. F. A. P. Miller ◽  
J. Sprent
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Antibody Response ◽  
B Cell ◽  
Cell Population ◽  
Thoracic Duct ◽  
Secondary Antibody ◽  
Cba Mice ◽  
Duct Cells

Collaboration between thymus-derived lymphocytes and nonthymus-derived antibody-forming cell precursors occurs in the primary antibody response of mice to heterologous erythrocytes and serum proteins. The purpose of the experiments reported here was to determine whether collaboration took place in an adoptive secondary antibody response. A chimeric population of lymphocytes was produced by reconstituting neonatally thymectomized CBA mice soon after birth with (CBA x C57BL)F1 thymus lymphocytes. These mice could be effectively primed to fowl immunoglobulin G (FγG) and their thoracic duct lymphocytes adoptively transferred memory responses to irradiated mice. The activity of these cells was impaired markedly by preincubation with CBA anti-C57BL serum and to a lesser extent by anti-θ-serum. Reversal of this deficiency was obtained by adding T cells in the form of thoracic duct cells from normal CBA mice. Cells from FγG-primed mice were at least 10 times as effective as cells from normal mice or from CBA mice primed to horse erythrocytes. These results were considered to support the concept that memory resides in the T cell population and that collaboration between T and B cells is necessary for an optimal secondary antibody response. Poor antibody responses were obtained in irradiated mice given mixtures of thoracic duct cells from primed mice and of B cells from unprimed mice (in the form of spleen or thoracic duct cells from thymectomized donors). In contrast to the situation with T cells, the deficiency in the B cell population could not be reversed by adding B cells from unprimed mice. It was considered that memory resides in B cells as well as in T cells and that priming probably entails a change in the B cell population which is fundamentally different from that produced in the T cell population.

scholarly journals MATURATION OF B LYMPHOCYTES IN THE RAT

1973 ◽  
Vol 138 (6) ◽  
pp. 1331-1344 ◽  
Author(s):  
Samuel Strober ◽  
Jeanette Dilley
Keyword(s):  
B Cells ◽  
B Lymphocytes ◽  
Thoracic Duct ◽  
Time Course ◽  
Turnover Rate ◽  
Bone Marrow Cells ◽  
Thoracic Duct Lymph ◽  
Duct Cells ◽  
Turn Over ◽  
Marrow Cells

The migration pattern, tissue distribution, and turnover rate of unprimed and primed B lymphocytes involved in the adoptive anti-DNP response was studied. The adoptive primary response restored by unprimed spleen or thoracic duct cells passaged through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) was markedly diminished as compared with that restored by unpassaged cells. On the other hand, the adoptive response restored by passaged spleen or thoracic duct cells from DNP-primed donors was greater than or the same as that restored with unpassaged cells, respectively. This suggests that unprimed B cells change from nonrecirculating to recirculating lymphocytes after exposure to antigen. Studies of the adoptive anti-DNP response restored by unprimed or primed bone marrow cells showed little change in the time-course or amplitude of the response restored by either population of cells. The relative inability of marrow cells to carry immunological memory was related to the inability of recirculating memory cells to penetrate the marrow. The turnover rate of unprimed and primed B cells was investigated by treating the cell donors with [3H]thymidine for 48 h before removal of thoracic duct or spleen cells. The adoptive anti-DNP response restored by unprimed or primed cells was not affected by [3H]thymidine treatment. This indicates that both populations of cells turn over slowly. However, our previous studies show that unprimed B cells involved in the adoptive antibody response to ferritin turn over rapidly. The different findings are discussed in the context of antigen-dependent B-cell maturation.

scholarly journals INITIATION OF ANTIBODY RESPONSES BY DIFFERENT CLASSES OF LYMPHOCYTES

1969 ◽  
Vol 130 (4) ◽  
pp. 895-906 ◽  
Author(s):  
Samuel Strober
Keyword(s):  
Antibody Response ◽  
Thoracic Duct ◽  
Salmonella Typhi ◽  
Primary Response ◽  
Primary Antibody ◽  
Spleen Cells ◽  
Normal Cells ◽  
Duct Cells ◽  
Primary Antibody Response

Thoracic duct cells and spleen cells were tested for their ability to restore the primary antibody response of X-irradiated rats to bovine serum albumin (BSA), sheep red blood cells (SRBC), horse spleen femtin (HSF), and Salmonella typhi flagella. Spleen cells were at least as efficient as thoracic duct cells in restoring the response to BSA, HSF, and Salmonella typhi flagella. In further experiments thoracic duct cells lacking large dividing lymphocytes were tested for their ability to restore the primary response. Large lymphocytes were eliminated by the in vitro incubation of thoracic duct cells for 24 hr at 37°C or by treatment of thoracic duct cell donors with the mitotic inhibitor vinblastine sulfate 24 hr prior to cannulation of the thoracic duct. Experiments with SRBC show that incubated cells and cells from vinblastine-treated donors are as efficient as normal cells in restoring the primary antibody response. On the other hand, experiments with HSF and Salmonella typhi flagella show that incubated cells and cells from vinblastine-treated donors are about five times less efficient than normal cells in restoring the response. Normal thoracic duct cells were more efficient than incubated cells but less efficient than cells from vinblastine-treated donors in restoring the early response to BSA. The experimental findings indicate that the classes of thoracic duct lymphocytes which initiate the primary antibody response to SRBC differ from the classes which initiate the response to HSF and Salmonella typhi flagella, or BSA.

scholarly journals Highly mutated memory cells drive an inefficient secondary antibody response to a variant protein

2018 ◽  
Author(s):  
Richard K Tennant ◽  
Barbara Holzer ◽  
John Love ◽  
Elma Tchilian ◽  
Harry N White
Keyword(s):  
B Cells ◽  
Antibody Response ◽  
Primary Response ◽  
Affinity Maturation ◽  
Memory B Cells ◽  
Secondary Antibody ◽  
Cell Compartment ◽  
Related Proteins ◽  
Serum Response ◽  
Variant Protein

AbstractA powerful vaccine against mutable viruses might induce memory antibodies that either strongly bound antigenic variants or that could rapidly undergo secondary affinity maturation to achieve this. We have recently shown after secondary immunization of mice with a widely variant protein (Burton et al. 2018) that IgM+ memory B-cells with few mutations supported an efficient secondary germinal centre (GC) and serum response, superior to a primary response to the same protein. Here, boosting with more closely related proteins produced a GC response dominated by highly mutated B-cells that failed, not efficiently improving serum avidity even in the presence of extra adjuvant, and that was worse than a primary response. This supports a hypothesis that over certain antigenic differences, a cross reactive, mutated, memory B-cell compartment can be an impediment to affinity maturation.

scholarly journals THE X-Y-Z SCHEME OF IMMUNOCYTE MATURATION

1968 ◽  
Vol 127 (2) ◽  
pp. 307-325 ◽  
Author(s):  
Vera S. Byers ◽  
Eli E. Sercarz
Keyword(s):  
Lymph Node ◽  
Antibody Response ◽  
Lymph Nodes ◽  
Large Dose ◽  
Primary Response ◽  
Memory Cells ◽  
Secondary Antibody ◽  
Booster Injection

A set of conditions has been described under which primed rabbit lymph nodes produce a secondary antibody response upon in vivo stimulation with a large dose of antigen, but are subsequently "exhausted;" that is, lymph node cultures prepared at intervals following the booster injection cannot be re-stimulated to display tertiary responses. Rabbits given 100-fold less antigen in the booster inoculum were able to give a tertiary response upon in vitro challenge. The system used permits neither induction nor continuation of a primary response to BSA in vitro. Since it could be demonstrated that no memory cells were generated by the booster injection within the intervals between in vivo injection and culture, the tertiary response in nonexhausted nodes must have been due to residual memory cells which remained untriggered by the in vivo booster injection. The unresponsive state was not caused by antibody feedback. These results are interpreted to mean that a population of memory cells can be exhausted by a supraoptimal dose of antigen, rendering the node temporarily incapable of further response. This implies that long-lived memory is not due to asymmetric division of memory cells. The source and fate of memory cells is discussed with regard to this evidence.

scholarly journals Prolonged survival in vivo of unprimed B cells responsive to a T-independent antigen.

1985 ◽  
Vol 161 (6) ◽  
pp. 1581-1586 ◽  
Author(s):  
Y Ron ◽  
J Sprent
Keyword(s):  
Lymph Node ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Thoracic Duct ◽  
Thoracic Duct Lymph ◽  
Cell Transfer ◽  
Adult Mice ◽  
Duct Lymph

Despite earlier evidence to the contrary, it has recently been claimed that most B lymphocytes, including lymph node (LN) and thoracic duct B cells, are short-lived cells of recent marrow origin. To seek direct information on this question, we transferred unprimed LN or thoracic duct B cells from normal mice to xid mice, i.e., mice unresponsive to the T-independent antigen, trinitrophenyl (TNP)-Ficoll. At varying periods after B cell transfer the recipients were challenged with TNP-Ficoll; anti-TNP plaque-forming cells were assayed in the spleen 6 d later. The results showed that the B cell recipients retained responsiveness to TNP-Ficoll for at least 3 mo after transfer. Responsiveness increased within the first 3 wk but then remained relatively constant. These findings imply that, at least for TNP-Ficoll-reactive cells, B cells residing in LN and thoracic duct lymph are not short-lived cells of recent marrow. Indeed, the data suggest that once the pool of recirculating B cells is fully formed in adult mice, further input of newly formed cells from the marrow into the recirculating pool is very limited.

scholarly journals the relationship between surface immunoglobulin isotype and immune function of murine B lymphocytes. III. Expression of a single predominant isotype on primed and unprimed B cells

1978 ◽  
Vol 147 (5) ◽  
pp. 1374-1394 ◽  
Author(s):  
I Zan-Bar ◽  
ES Vitetta ◽  
F Assisi ◽  
S Strober
Keyword(s):  
B Cells ◽  
Bovine Serum Albumin ◽  
Antibody Response ◽  
B Lymphocytes ◽  
Primary Response ◽  
Spleen Cells ◽  
Cell Sorter ◽  
Immunoglobulin Isotype ◽  
Surface Immunoglobulin ◽  
The Relationship

We determined whether primed and unprimed B cells in the spleen of (BALB/c × C57BL/Ka)F(1) mice contain subpopulations that express a predominant surface Ig isotype. Spleen cells were stained for surface isotypes and sorted on the fluorescence-activated cell sorter (FACS) in order to obtain B cells bearing predominantly IgM (μp cells), IgD (δp cells), or IgG (γp cells). Each population was assayed for its capacity to restore the adoptive primary and secondary anti-bovine serum albumin (BSA) antibody response in irradiated syngeneic recipients. In addition, the adoptive response restored by isotype-predominant cells was compared to that restored by isotype- positive cells (B cells bearing a given surface isotype alone or in combination with others). The experimental results show that μp cells restore the adoptive primary and secondary IgM and IgG responses to BSA, and γP cells restore only the primary and secondary IgG response. Δp Cells restored the adoptive secondary IgG response, but failed to restore the adoptive primary response at the cell doses tested. ΓP Cells but not δp cells suppressed the IgM response of the μ(+) and δ(+) cells. The contribution of isotype-predominant cells to both the adoptive primary and secondary anti-BSA response was smaller than that of B cells bearing a combination of surface isotypes. Differences in the Ig isotype pattern expressed on the surface of primed and unprimed B cells are discussed.

scholarly journals THE CARRIAGE OF IMMUNOLOGICAL MEMORY BY SMALL LYMPHOCYTES IN THE RAT

1966 ◽  
Vol 124 (5) ◽  
pp. 1017-1030 ◽  
Author(s):  
James L. Gowans ◽  
Jonathan W. Uhr
Keyword(s):  
Thoracic Duct ◽  
Immunological Memory ◽  
Antibody Responses ◽  
Thoracic Duct Lymph ◽  
Primary Immunization ◽  
Duct Cells ◽  
Duct Lymph ◽  
Secondary Type ◽  
Rapid Antibody

Lymphocytes were obtained from the thoracic duct of rats 1½ to 15 months after primary immunization with a single dose of bacteriophage ϕX 174. An intravenous injection of these lymphocytes conferred on heavily X-irradiated rats the ability to form antibody in a secondary-type manner after a first injection of ϕX. Negligible responses were obtained after cell transfer if the recipients were not challenged with antigen. Thoracic duct cells from some immunized donors were incubated in vitro for 24 hr before transfer in order to destroy selectively the large, dividing lymphocytes. The responsiveness conferred on X-irradiated recipients by such "incubated" inocula was then compared with that given by equal numbers of "fresh" thoracic duct cells. In all such comparisons the recipients of the "incubated" cells gave higher and more rapid antibody responses. It was concluded that the cells in thoracic duct lymph which carried immunological memory were small lymphocytes.

scholarly journals The requirement for C3 receptors on the precursors of 19S and 7S antibody-forming cells.

1976 ◽  
Vol 143 (5) ◽  
pp. 1111-1121 ◽  
Author(s):  
D W Mason
Keyword(s):  
T Cell ◽  
B Cells ◽  
Antibody Response ◽  
B Cell ◽  
Adoptive Transfer ◽  
Thoracic Duct ◽  
Transfer System ◽  
C3 Receptors ◽  
Cell Cooperation

The main conclusion from this study is that C3 receptors are not required for the generation from B cells of a thymus-dependent 7S antibody response. The requirement for C3 receptors on the precursors of antibody-forming cells was studied in an adoptive transfer system using thoracic duct lymphocytes (TDL) from primed rats as a source of precursors and irradiated recipients as hosts. 7S precursors were found in both the CR+ and the CR- fractions of TDL and it was established that the response transferred by CR- cells did not arise from either a raidoresistant B cell in the host or from CR+ cells contaminating the CR- population. Thus, the C3 receptor is not obligatory for B-cell-T-cell cooperation in the 7S response. The precursors of 19S antibody-forming cells were found only in the CR+ subpopulation. The CR-Ig+ subpopulation was shown to contain all the B blasts in rat TDL and a very small number (approximately 1% of all TDL) of small lymphocytes. This latter population contained the CR- 7S precursors and contributed approximately 20% of the total adoptive secondary 7S response transferred by CR+ and CR- subpopulations combined. This observation suggests that the percentage of rat TDL committed to carry 7S memory is small, a conclusion which is confirmed and extended in the following paper.

scholarly journals Anti-idiotype induced regulation of helper cell function for the response to phosphorylcholine in adult BALB/c mice.

1978 ◽  
Vol 148 (5) ◽  
pp. 1216-1227 ◽  
Author(s):  
K Bottomly ◽  
B J Mathieson ◽  
D E Mosier
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Antibody Response ◽  
Gamma Globulin ◽  
Cell Function ◽  
Keyhole Limpet Hemocyanin ◽  
Secondary Antibody ◽  
Suppressor T Cells ◽  
Helper Activity

An adoptive secondary antibody response to phosphorylcholine (PC) can be generated by the transfer of keyhole limpet hemocyanin (KLH)-primed T cells, PC-bovine gamma globulin-primed B cells, and PC-KLH into irradiated syngeneic BALB/c mice. If the KLH-primed T-cell donors were pretreated with anti-idiotype antibodies directed against the BALB/c PC-binding myeloma TEPC 15, their T cells were unable to collaborate effectively with PC-primed B cells; moreover, they could suppress the helper activity of T cells from normal mice for the PC-KLH response. The Ly phenotype of these T cells was found to be Ly 1-, 2+. The specificity of the suppressor T-cell population induced by anti-T15 treatment appears to be both for idiotype (hapten) and carrier, since the suppressor T cells fail to interfere with the antibody response to PC on a heterologous carrier, nor do they suppress the response to trinitrophenol-KLH.

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