Secretion of immunoglobulin by neoplastic B lymphocytes from lymph nodes of patients with lymphoma

Stevenson, F K; Gregg, Evan O.; Smith, Joan K.; Stevenson, G T

doi:10.1038/bjc.1984.224

Cited by 17 publications

(3 citation statements)

References 13 publications

(9 reference statements)

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“…This raises the question of whether B lymphoma cells in patients secrete Ig in sufficient amounts to efficiently prime tumor-infiltrating APC for initiation of Id-specific CD4 þ T-cell responses. While previous reports suggest modest secretion of complete Ig in B-cell malignancies including chronic lymphocytic leukemia and non-Hodgkin's lymphoma (34,35), other studies indicate that a significant release of free Ig L chain may occur in such patients (36,37). The latter observation is noteworthy, given recent data from our group showing that uptake and presentation of free L chains by tumor-infiltrating macrophages is approximately 100-fold more efficient compared with complete Ig (20,38).…”

Section: Discussionmentioning

confidence: 89%

CD4+ T-cell–Mediated Rejection of MHC Class II–Positive Tumor Cells Is Dependent on Antigen Secretion and Indirect Presentation on Host APCs

et al. 2018

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Tumor-specific CD4 T cells have been shown to mediate efficient antitumor immune responses against cancer. Such responses can occur through direct binding to MHC class II (MHC II)-expressing tumor cells, or indirectly via activation of professional antigen-presenting cells (APC) that take up and present the tumor antigen. We have previously shown that CD4 T cells reactive against an epitope within the Ig light chain variable region of a murine B-cell lymphoma can reject established tumors. Given the presence of MHC II molecules at the surface of lymphoma cells, we investigated whether MHC II-restricted antigen presentation on tumor cells alone was required for rejection. Variants of the A20 B lymphoma cell line that either secreted or intracellularly retained different versions of the tumor-specific antigen revealed that antigen secretion by the MHC II-expressing tumor cells was essential both for the priming and effector phase of CD4 T-cell-driven antitumor immune responses. Consistent with this, genetic ablation of MHC II in tumor cells, both in the case of B lymphoma and B16 melanoma, did not preclude rejection of tumors by tumor antigen-specific CD4 T cells These findings demonstrate that MHC class II expression on tumor cells themselves is not required for CD4 T-cell-mediated rejection and that indirect display on host APC is sufficient for effective tumor elimination. These results support the importance of tumor-infiltrating APC as mediators of tumor cell killing by CD4 T cells. Elimination of tumors by CD4 T cells recognizing secreted tumor neoantigens can occur in the absence of tumor cell-intrinsic MHC II expression, highlighting the potential clinical relevance of indirect antigen recognition by tumor-infiltrating APC. http://cancerres.aacrjournals.org/content/canres/78/16/4573/F1.large.jpg .

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Section: Discussionmentioning

confidence: 89%

CD4+ T-cell–Mediated Rejection of MHC Class II–Positive Tumor Cells Is Dependent on Antigen Secretion and Indirect Presentation on Host APCs

et al. 2018

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“…show bidirectional differentiation; a further 200 cases of CLL (Hamblin et a1 (16) and unpublished data) and 250 cases of non-Hodgkin's lymphoma (unpublished data) were screened and none of these showed an overlap in T3 and SIg expression. As measured by methods described by Stevenson et a1 (34) blood lymphocytes from the patient with CLL (T.S.) cultured in vitro produced IgK (28 ng/ml) (unpublished data) which is in keeping with the Ig surface phenotype of the CLL cells; Igh was not detected in the culture supernatants.…”

Section: Discussionmentioning

confidence: 72%

Co‐expression of T3 and surface immunoglobulin in neoplasms of ‘early’ B cells: A report of 2 cases

Haegert

Smith

1987

European J of Haematology

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Chronic lymphocytic leukaemia (CLL) and well-differentiated lymphocytic lymphoma (WDLL) characteristically express surface membrane immunoglobulin (SIg) and react with monoclonal antibodies (Mabs) directed against a marker present on most normal T cells, namely TI. These SIg-positive B cells are usually negative for other T cell markers including T3 (CD3) which is expressed in all normal T cells. We report 2 cases, 1 CLL and 1 WDLL, in which the peripheral lymphocytes not only expressed monotypic SIg but also reacted with the T3-specific Mabs UCHTl and OKT3 by indirect immunofluorescence or immunoperoxidase staining. False-positive staining by both UCHTl and OKT3 was excluded by showing that lymphocytes sensitized with an irrelevant mouse Mab did not stain with second layer antibodies and that lymphocytes stained with second layer antibodies alone were always completely unreactive. Also, in 1 case the determinants demonstrated by both anti-Ig and UCHTl were re-expressed after capping and shedding, i.e. appeared to be endogenous. The B cell origin of the CLL lymphocytes was supported by the finding of CK gene rearrangement in the absence of T, gene rearrangement. It seems therefore that neoplasms of 'early' B cells may show bidirectional differentiation and co-express markers that are believed to be T-specific.Chronic lymphocytic leukaemia (CLL) and welldifferentiated lymphocytic lymphoma (WDLL) are closely related diseases that most commonly represent neoplastic B-cell proliferations (1). These B cells typically express monotypic surface immunoglobulin (SIg) and react with monoclonal antibodies against T1 (2); T1 (CD5) is a T-cell

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“…However, the splenectomy and peripheral blood analyses were carried out on different dates (see Table 1) and there is evidence that the surface phenotype of HCs may change over time (6). As measured by methods described by Stevenson et al (29), spleen cells from B. C. and blood cells from F. B. cultured in vitro produced IgK (42 ng/ml and 7 ng/ml, respectively) (unpublished data), which is in keeping with the Ig surface phenotype; Igh was not detected in the culture supernatants. Spleen cells from C. S. produced 19 ng IgK/ml and 650 ng Igh/ml in culture (unpublished data); a marked excess of Igh is consistent with the neoplastic cell surface phenotype.…”

Section: Discussionmentioning

confidence: 81%

Co‐expression of surface immunoglobulin and T3 on hairy cells

Haegert

Furlong

Smith

1986

Scandinavian Journal of Haematology

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Whereas it is generally believed that most cases of hairy cell leukaemia (HCL) represent B cell neoplasms, it is reported here that 4 of 14 cases of HCL not only express monotypic surface immunoglobulin (SIg) but also react with the T cell‐specific monoclonal antibody (Mab) UCHT1 by indirect immunofluorescence or immunoperoxidase staining. Although both UCHT1 and OKT3 recognize the T3 molecule, which is expressed in all normal T cells, UCHT1+ hairy cells (HCs) were consistently OKT3−. Spurious reactivity of UCHT1 antibodies with SIg+ HCs was excluded by showing that lymphocytes sensitized with an irrelevant mouse Mab did not stain with second layer antibodies and lymphocytes sensitized with second layer antibodies alone were always completely unreactive. Moreover, in 1 case the determinants demonstrable by both UCHT1 and anti‐Ig were strongly re‐expressed after capping and shedding, i.e. appeared to be endogenous. It is concluded that HCs with a hybrid T‐B surface phenotype are more common than hitherto reported, that HCs may express T3 molecules as well as SIg but that determinants recognized by OKT3 may be cryptic or buried in the HC membrane.

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Secretion of immunoglobulin by neoplastic B lymphocytes from lymph nodes of patients with lymphoma

Abstract: Summary An investigation has been made into the ability of neoplastic B lymphocytes obtained from lymphoid tissue of patients with non-Hodgkin's lymphoma (NHL) to secrete immunoglobulin (Ig) in vitro.

Cited by 17 publications

References 13 publications

CD4+ T-cell–Mediated Rejection of MHC Class II–Positive Tumor Cells Is Dependent on Antigen Secretion and Indirect Presentation on Host APCs

CD4+ T-cell–Mediated Rejection of MHC Class II–Positive Tumor Cells Is Dependent on Antigen Secretion and Indirect Presentation on Host APCs

Co‐expression of T3 and surface immunoglobulin in neoplasms of ‘early’ B cells: A report of 2 cases

Co‐expression of surface immunoglobulin and T3 on hairy cells

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