B lymphocytes as effector cells in the immunotherapy of cancer

Abstract

Over the years, the role of B cells in the host immune response to malignancy has been overshadowed by our focus on T cells. Nevertheless, B cells play important roles as antigen-presenting cells and in the production of antibodies. Furthermore, B cells can function as effector cells that mediate tumor destruction on their own. This review will highlight the various functions of B cells that are involved in the host response to tumor.

Figure 1

Activated B cells from tumor-draining lymph nodes (TDLN) mediate tumor regression after adoptive transfer in mice bearing 3-day established lung metastases. In these two separate experiments groups of mice (n=6) received activated T cells alone, B cells alone, or a combination of both. Mean number of pulmonary metastases (±SEM) at the end of the experiments are depicted in the graphs. The combination of T and B cells was superior to all other groups. (From Li et al.)

Figure 2

Activated B cells from TDLN can cause tumor cell cytolysis in an immunologically specific fashion. 4T1 TDLN B cells were secondarily activated with LPS/anti-CD40 and evaluated for cytotoxicity using an LDH release assay. Activated B cells were admixed with tumor cells at different effector: target (E:T) ratios and the amount of killing was assessed. 4T1 TDLN B cells were able to kill 4T1 tumor cells, and not the irrelevant Renca or TSA tumors as shown in these two separate experiments. (From Li et al.)

Figure 3

Activated B cells induce tumor reactive T cell responses in tumor-bearing hosts. Mice bearing 4T1 tumor were treated with activated B cells, IL-2 or no treatment. Spleens of the mice were harvested and splenic T cells activated in vitro. These activated splenic T cells were tested for tumor reactivity by measuring IFNγ release when mixed with irradiated tumor cells. Mice that received activated 4T1 TDLN B cells were found to have splenic T cells reactive to 4T1 tumor cells, and not to irrelevant tumor cells indicating the ability of activated B cells to present antigen to the secondary host. (Li et al.)

Figure 4

Activated TDLN B cells produce antibody that can mediate complement dependent cytotoxicity (CDC). Supernatants (Sup) from activation cultures of D5 and MCA 205 TDLN B cells were tested for their ability to mediate CDC in vitro. Pan-02 was used as an irrelevant tumor cell control. As can be seen, the supernatants contained antibodies that were able to specifically lyse the relevant tumor targets. (Li et al.)

Figure 5

TDLN B cell-produced IgG2b binds specifically to tumor cells. D5, MCA 205, and Pan-02 tumor cells were incubated with the culture supernatant (Sup) of MCA 205 TDLN B cells. Bound IgG2b onto tumor cells was then detected by a secondary antibody, FITC-anti-mouse IgG2b. FITC-coupled isotype-matched control was used to measure background staining. (Li et al.)

Figure 6

Antibodies produced by activated D5 TDLN B cells can bind to unique epitopes from the lysate of D5 tumor cells and not to other tumor lysates. Supernatants from activated D5 TDLN T cells and B cells were admixed with the lysates of D5, MCA 205 and Pan-02 tumor cells. The immunoprecipitates were then run on an SDS-PAGE gel. Unique bands were identified in the lane were antibodies produced by activated D5 TDLN B cells were admixed with D5 tumor lysate.(Namm et al. unpublished data).

Figure 7

Schematic illustration of B cell interactions related to tumor. Abbreviations: CpG (cytosine phosphodiester guanine oligodeoxynucleotides); LPS (lipopolysaccharides); anti-CD40 (anti-CD40 monoclonal antibody); ADCC (antibody dependent cellular cytotoxicity); and CDC (complement dependent cytotoxicity).