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Biomedical subjects

M H Julius

Publications and source records attributed to M H Julius.

At least 37 records · Page 2Linked to original sources
PubMed1983

Thymus-independent induction and antigen-dependent recovery of idiotype-specific suppression.

BALB/c nude (nu/nu) mice and euthymic (nu/+) littermates were treated as neonates with anti-T15 antibody and challenged at various ages with either a thymus-independent, PC-Brucella abortus (PC-BA), or thymus-dependent, PC-keyhole limpet hemocyanin (PC-KLH), form of phosphorylcholine (PC). Nu/nu mice challenged with PC-KLH received KLH-primed splenic T cells prior to immunization. Neither neonatally anti-idiotype-treated nu/+ nor nu/nu mice responded with the production of T15-positive anti-PC antibodies after challenge with either form of PC antigen. It is concluded that neither induction nor maintenance of a state of T15-specific suppression requires thymus-matured T cells. Recovery of anti-PC responsiveness in suppressed nu/+ or nu/nu mice was similar and was found to be related to the form of antigen used to elicit the response. Immunization with PC-KLH revealed a long-lasting unresponsiveness (up to 16 weeks). In contrast, immunization with PC-BA elicited a full anti-PC response as early as at 6.5 weeks of age.

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PubMed1983

Two classes of bystander B cell response: activation requirements reflect those of B cells in general.

Bystander anti-sheep red blood cell (SRBC) antibody responses were induced in cultures containing unprimed B cells, SRBC, particulate or soluble eliciting antigen, and helper T (Th) cells primed to the eliciting antigen. The use of long-term cultured Th cells, depleted of alloreactive cells, allowed direct assessment of the requirements for major histocompatibility complex- (MHC) restricted interactions in the cellular events leading to bystander B cell activation. H-2 restricted Th cell activation limited all bystander B cell responses; however, the requirement for H-2 restricted Th-B cell interactions varied with the state of activation of the responding B cell population before assay. Thus, we defined two classes of bystander B cell response. Activation of small (i.e., resting) SRBC-specific bystander B cells, purified by density gradient centrifugation, was completely restricted by B cell MHC. The requirement for high concentrations of eliciting antigen suggests that nonspecific binding of soluble or particulate antigen to the responding B cell surface plays a mandatory role leading to the activation of resting bystander B cells. The concomitant requirement for a restricted Th-B cell interaction suggests that this role is one of focusing antigen-specific, H-2 restricted T cell help to the resting B cell. In contrast, bystander responses, unrestricted by B cell MHC, were generated exclusively from large (i.e., blasted) B cells limited only by Th cell activation. This class of SRBC-specific bystander response correlated with an SRBC-dependent increase in the number of cells secreting antibodies that recognized degraded mouse RBC. Thus, we propose that the H-2 unrestricted anti-SRBC response is derived from the amplification of B cells activated in vivo to degraded homologous RBC. Both classes of anti-SRBC response were enhanced by the presence of the bystander antigen. This phenomenom is discussed in terms of a mitotic advantage provided by the interaction of antigen with surface immunoglobulin on specific bystander B cells.

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PubMed1982

Dissociation of two signals required for activation of resting B cells.

Cellular interactions involved in the T cell-dependent activation of B cells were analyzed by using lines and clones of helper T cells specific for determinants expressed on the B cell surface. Activation of male antigen-, M locus-, and H-2-specific T cells was shown to support polyclonal Ig production by a population of B cells that did not require T-cell-B-cell interaction for induction/amplification. However, these T cells alone did not activate gradient-purified small (resting) B cells. The activation of small B cells was shown to require not only a signal derived through an antigen-specific T-helper cell-B cell interaction but in addition a second signal that could be provided by anti-Ig antibodies.

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PubMed1981

The mechanism of thymus-dependent antibody formation in bone marrow.

During the primary immune response of mice to i.v. administered thymus-dependent antigens the spleen is the major site of localization of antibody-producing plaque-forming cells (PFC). During the secondary response, on the other hand, large numbers of PFC not only appear in the spleen, but also in the bone marrow. By inducing B memory cells with a DNP-carrier complex and activating the DNP-specific B memory cells with the same hapten conjugated to a heterologous carrier, we show in this paper that B memory cells, but not necessarily T memory cells, must be present before booster immunization for PFC to appear in the bone marrow. The origin of the PFC that appear in the bone marrow during secondary type immune response was studied in parabiotic mice consisting of members congenic for the Igh-1 locus. From analysis of the allotype of antibodies produced by PFC in the marrow of such pairs of parabionts it appeared that antibody formation in bone marrow is dependent on the immigration into the marrow of B memory cells activated in peripheral lymphoid organs. Consistent with such a migration of activated cells, radioautographic studies in guinea pigs demonstrated an influx of newly formed mononuclear cells into the bone marrow via the blood stream during the first 3 days after intravascular antigen administration.

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PubMed1980

Enrichment of hapten-specific helper T cells using anti-immunoglobulin combining site antibodies.

Spleen T cells from phosphorylcholine (PC)-primed BALB/c mice were indirectly stained with affinity column-purified heterologous rabbit anti-TEPC 15 (T 15) antibodies. These antibodies were shown to be directed towards antigenic determinants in or near the combining site of T 15 in that their interaction with the myeloma protein was more than 95% inhibitable by PC. The stained cells were sorted into "bright" and "dull" fractions using a fluorescence-activated cell sorter. Sorted populations were then assessed for enrichment and depletion of PC-specific helper activity using an in vivo adoptive transfer assay. The results indicate that the staining procedure employed enabled the specific enrichment of PC helper T cells and therefore suggest that these T cells bear combining site structures similar to that of the myeloma protein T 15.

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PubMed1979

Helper activity of T cells stimulated in long-term culture.

Thymus-derived (T) cells obtained from three categories of in vitro antigen-induced proliferative responses were assayed as sources of helper T cells. These categories are exemplified by (a) direct stimulation of keyhole limpet hemocyanin (KLH)-primed cell with KLH, which results in high indexes of proliferation; (b) direct stimulation of apoferritin-primed cells with apoferritin, which does not result in indexes of proliferation above background levels; (c) trans-stimulation of unprimed cells with X-irradiated KLH-primed cells which results in indexes of proliferation comparable to category (a). Our results indicate that levels of [3H]thymidine incorporation by proliferating populations are not an accurate reflection of helper T cell generation. Directly stimulated KLH and apoferritin-primed cells give rise to highly enriched populations of antigen-specific helper T cells which support both IgM and IgG antibody responses in vitro. Moreover, these specific helper T cells are functionally restricted by products encoded by the I region of the major histocompatibility complex (MHC). Helper T cells generated in KLH-trans-stimulated cultures are not KLH-specific in that comparable levels of helper activity are expressed using either KLH or apoferritin as carriers. These non-KLH-specific helper T cells only support the production of IgM antibody in vitro and they are not functionally restricted by MHC products.

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PubMed1978

Evidence for the endogenous production of T cell receptors bearing idiotypic determinants.

Unprimed thymus-derived (T) cells from spleens of either conventional TEPC 15+ (T15+) BALB/c mice or neonatally suppressed T15- BALB/c mice were used to reconstitute neonatally suppressed T15- BALB/c nude mice and conventional T15+ BALB/c nude mice, respectively. In so doing, the idiotypes produced by phosphorycholine (PC)-specific bone marrow-derived (B) cells were dissociated from idiotypes putatively produced by PC-specific T cells. Subsequent to priming of the reconstituted BALB/c nude mice with either anti-T15 antisera or PC-MOPC 315, their splenic T cells were assessed for PC-specific helper activity and expression of the T15 idiotype. Our results indicate that expression of the T15 idiotype by T cells as determined by (a) the ability to prime PC-specific helper cells with anti-T15 antibodies, and (b) the ability to inhibit PC-specific helper function with anti-T15 antibodies, depended on the idiotype of the unprimed donor T cell source and not that of the B cells in the reconstituted recipients. We conclude that the idiotype-bearing T cell receptor specific for PC is not a passively adsorbed B cell product.

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PubMed1978

Behaviour of sheep-immunoglobulin-bearing and non-immunoglobulin-bearing lymphocytes isolated by nylon wool columns.

The technique of separating lymphocytes on nylon wool columns has been applied to sheep lymphocytes obtained from efferent lymph. The non-immunoglobulin-bearing (sIg-) lymphocytes which pass through the column were MLR-reactive, responsive only to T cell mitogens, and migrated in vivo like T lymphocytes described in rodents. Immunoglobulin-bearing (sIg+) lymphocytes were MLR-non-reactive, responsive to lipopolysaccharide and migrated in vivo like B lymphocytes in rodents. It is considered that the majority of sIg- lymphocytes obtained in this way are T lymphocytes and the majority of sIg+ lymphocytes are B lymphocytes.

Animals↗
PubMed1977

Induction and characterization of "autologous" anti-isiotypic antibodies.

Upon immunization with phosphorylcholine (PC), conventional BALB/c mice produce anti-PC antibodies bearing predominantly the idiotype characteristic of the BALB/c PC-binding myeloma protein TEPC 15 (T15). To investigate whether BALB/c mice are able to produce antibodies to the autologous T15 idiotype, conventional (T15-positive) and neonatally suppressed (T15-negative) BALB/c mice were immunized with purcific for the T15 idiotype. However, anti-T15 antibodies were more readily induced in neonatally suppressed mice which in turn produced higher anti-T15 titers than conventional mice. Such "autologous" anti-T15 antibodies are able to (a) change the idiotypic pattern of the anti-PC response of conventional BALB/c mice in situ and, (b) inhibit the induction of an anti-PC response in vitro by spleen cells from T15-positive but not T15-negative BALB/mice. Thus, BALB/c mice are capable of producing anti-T15 antibodies upon immunization with an isologous myeloma protein which bears the autologous T15 isiotype. We suggest that isiotypes should not be strictly considered as "self-antigens" since the dramatic increase in their concentration, subsequent to antigen stimulation, might confer upon them immunogenic properties not shared by self-antigens.

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PubMed1976

Isolation of antigen-binding cells from unprimed mice. II. Evidence for monospecificity of antigen-binding cells.

Spleen cells from unimmunized mice were exposed to two contrastingly fluorescent antigens simultaneously. Antigen-binding cells of either specificity were isolated using a fluorescence-activated cell sorter (FACS). Purified cells binding one or the other of the antigens were then examined by fluorescence microscopy for the presence of bound antigen of the alternate specificity. No double binding cells were seen. If cells bear receptors of two or more specificities and these receptors are randomly distributed among antigen-binding cells, then of the 13 000 binding cells examined 82 were expected to bind both antigens. These results strongly suggest that antigen-binding cells bear receptors of only one specificity. In addition, by inference from the functional correlation between antigen-binding cells and precursor cells, the data support the contention that precursors of antibody-forming cells are monospecific.

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