Purified Protein Derivative of Tuberculin Induces Immunoglobulin Production in Normal Mouse Spleen Cells

Abstract

Two major events occur in the response of the immune system to antigenic stimulation, proliferation of cells and secretion of soluble products. The relative importance of these two events is not well known. Mitogens have been found to provide valuable tools for analysis of these problems (for review, see reference 1). The substances most well studied are phytohemagglutinin (PHA) 1 and concanavalin A, which have been found to selectively activate thymus-derived (T) cells (2-6), and lipopolysaccharides of bacterial origin (LPS), which have been found to selectively activate bursal equivalent or bone marrow-derived (B) cells (2, 7). Pokeweed mitogen seems to activate both cell types (4).Recently we reported (8) that purified protein derivative (PPD) tuberculin, which has previously been associated only with a number of supposed T cell activities in immune situations, induces D N A synthesis in nonimmune mouse B cells, i.e., acts as a B cell mitogen. The present work reports our analysis of a second major activity of PPD, namely induction of immunoglobulin synthesis.

Regulatory Mechanism of Reagin Production in Mice at the T Cell Level

“…3). It seems possible that B cells specific for DNPdeterminant are stimulated directly with DNP-PPD in the absence of Tbc-primed cells since PPD itself reveals a mitogenic activity on B cells, thus acting as a polyclonal activator for the B cells (19,22). However, this was not the case in the present study since DNP-specific B cells in DNP-OVA-primed cells were not stimulated directly with DNP-PPD without Tbc-primed cells as shown in Fig.…”

Endotoxin protein: a B-cell mitogen and polyclonal activator of C3H/HeJ lymphocytes.

“…For polyclonal activation spleen cell cultures were prepared at cell concentrations of 10 x 10 ~ ml. 1 ml of the suspension was incubated in 35 mm plastic Petri dishes at 37°C in an atmosphere of 83% N2, 10% CO2, and 7% O~ with or without stimulants for a period of 48 h as previously described (19). Antibody-forming cells were enumerated by a modified hemolytic plaque assay (19) using trinitrophenyl (TNP)-conjugated sheep erythrocytes (SRBC).…”

Carrier-and hapten-antibody producing cells, in vitro II. Effect of purine antimetabolites

“…In this case, the maximum response occurred on days 3-4 compared to a maximum response on day 4 when normal spleen cells were cultured with TNP-HRBC [6]. The anti-TNP response observed on day 2 was relatively insensitive to 6-MP (i.e., [6,8,9,17]. Early appearance of APC after injection of the agents mentioned above suggested that APC arose from intermediate ~ late precursor cell types.…”